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There are several in vitro systems that enable evaluation of the absorption direction, but there are few quantitative systems that enable easy evaluation of the excretion direction. Enteroids, organoids derived from intestine, have been frozen and passaged for various research. But it is not clear how the freezing and passaging affect the expression and function of transporters. We investigated the effects of passage and cryopreservation of enteroids. We focused on P-gp (P-glycoprotein) and compared the transfer rates of rhodamine 123 (Rh123) into the lumen of enteroids with and without a P-gp inhibitor. mRNA expression levels did not change significantly before and after passage and cryopreservation. Accumulation of Rh123 in the lumen of enteroids was observed. With some P-gp inhibitors, excretion of Rh123 into the lumen of enteroids was inhibited and the nonexcreted Rh123 accumulated in enteroids epithelial cells. The transfer rate of Rh123 into the lumen of enteroids with a P-gp inhibitor was significantly decreased compared to that of without a P-gp inhibitor. Before and after passage and cryopreservation, the transfer rate was almost the same as that of primary cultured enteroids. We succeeded in easily evaluating whether a component is a substrate of P-gp using enteroids. [Display omitted] • mRNA expression level of efflux intestinal transporter was not changed before and after passage and number of culture days. • This method allows semi-quantitative evaluation of efflux transporters function regardless of the shapes of enteroids. • Our method enables to easily evaluate whether a component is a substrate of P-gp using enteroids. [ABSTRACT FROM AUTHOR]

Climbazole is an antimycotic compound used in cosmetic products as a preservative or as an active ingredient in anti-dandruff (AD) formulations. In this study we provide human toxicokinetic data on climbazole. Using our previously published analytical method, we investigated the urinary excretion of two climbazole metabolites, (OH) 2 -climbazole and cx-OH-climbazole, for 48 h after oral ingestion (n = 5, 49–77 µg/kg bw) and for 72 h after dermal application of either a climbazole-containing rinse-off AD shampoo or a leave-on hair tonic (n = 2×3). In total, 23.9 % (18.0–33.4 %) of the oral dose were excreted as the two abovementioned metabolites over 48 h. In one volunteer, who used an over-the-counter phytopharmaceutical, metabolite excretion was about three times lower and we found influences on diastereoselectivity of (OH) 2 -climbazole formation using a modified analytical method. After dermal application, urinary concentration maxima occurred considerably later than after oral intake. The two different dermal exposure scenarios also revealed a relevance of exposure duration and product formulation on the systemic availability of climbazole. Back-calculated oral-dose-equivalent intakes from the dermal exposures showed a maximum climbazole intake of 18.5 µg/kg bw/d after hair tonic use, or 6.6 µg/kg bw/d after AD shampoo application. • (OH) 2 -climbazole and cx-OH-climbazole identified as suitable exposure biomarkers. • On average 24 % of the dose were recovered in form of the investigated biomarkers within 48 h. • Shifting diastereomeric ratios observed within the investigated excretion period. • Sum parameter recommended as the most robust approach for reverse dosimetry. [ABSTRACT FROM AUTHOR]

We report a case of an 80-year-old woman with botulism from 2020 in Osaka, Japan. The patient complained of dysarthria and dizziness. On the same day, the patient developed respiratory failure, and was intubated and placed on mechanical ventilation. Subsequently, ophthalmoparesis and quadriparesis progressed rapidly. Ten days after onset, the patient failed to respond to any external stimulation. Blood tests showed anemia, and computed tomography revealed undiagnosed cervical cancer. Initially, diagnosis of neuromuscular junction disorder and acute motor neuropathy, including paraneoplastic syndrome, were considered. However, intravenous immunoglobulin therapy and plasma exchange were ineffective. A fecal sample on day 30 showed a large number of C. botulinum spores. On day 34, a mouse bioassay revealed botulinum toxin type A in the patient's serum; therefore, a botulinum antitoxin was administered. Later, the patient's muscle strength was gradually improved. However, severe muscle paralysis persisted, and the patient died of cachexia owing to cervical cancer on day 196. The etiology of this case was unknown because no contaminated food was identified during an inspection of the patient's home. Fecal 16S rRNA gene sequencing revealed dysbiosis of the intestinal microbiota with abundant Enterococcus species. Long-lasting excretion of substantial botulinum spores even on day 30 indicated colonization of C. botulinum in the intestinal tract. This case suggests that C. botulinum colonization with co-existing intestinal dysbiosis may be associated with severe and prolonged symptoms of botulism. [ABSTRACT FROM AUTHOR]

Including active renal excretion in physiologically based kinetic (PBK) models can improve their use in quantitative in vitro- in vivo extrapolation (QIVIVE) as a new approach methodology (NAM) for predicting the acute toxicity of organic cation transporter 2 (OCT2) substrates like paraquat (PQ). To realise this NAM, kinetic parameters Vmax and Km for in vitro OCT2 transport of PQ were obtained from the literature. Appropriate scaling factors were applied to translate the in vitro Vmax to an in vivo Vmax. in vitro cytotoxicity data were defined in the rat RLE-6TN and L2 cell lines and the human A549 cell line. The developed PQ PBK model was used to apply reverse dosimetry for QIVIVE translating the in vitro cytotoxicity concentration-response curves to predicted in vivo toxicity dose-response curves after which the lower and upper bound benchmark dose (BMD) for 50% lethality (BMDL 50 and BMDU 50) were derived by applying BMD analysis. Comparing the predictions to the in vivo reported LD 50 values resulted in a conservative prediction for rat and a comparable prediction for human showing proof of principle on the inclusion of active renal excretion and prediction of PQ acute toxicity for the developed NAM. [Display omitted] • A new approach methodology (NAM) predicting acute paraquat toxicity was defined. • This NAM included a newly developed PBK model with active renal excretion via OCT2. • Cytotoxicity data in lung epithelial cell lines were used for QIVIVE. • QIVIVE was based on PBK model based reverse dosimetry. • The in vivo dose response curves adequately predicted acute paraquat toxicity. [ABSTRACT FROM AUTHOR]

Drug elimination is the removal of active drug from the body. Metabolism takes place largely in the liver and produces water-soluble metabolites which can be excreted in the bile or urine. Metabolism may also produce active or toxic metabolites or a pharmacologically active drug from an inactive prodrug. Most volatile anaesthetics are excreted unchanged via the lungs. Drug elimination can be affected by factors such as first-pass metabolism, genetic variants and various disease processes. Knowledge of these processes will allow better prediction of pharmacokinetics in practice. [ABSTRACT FROM AUTHOR]

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug–drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug–drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired. GLP-1 receptor agonists and DPP-4 inhibitors are focused on GLP-1, an incretin peptide stimulate secretion of insulin. The physiological disposition of them is of great significance. [Display omitted] [ABSTRACT FROM AUTHOR]

The impact of β-glucan-rich oat bran on the bioavailability of orange juice (OJ) flavanones was investigated. Volunteers consumed 500 mL of OJ with and without 22 g of oat bran containing 6 g of β-glucan (OB-6). Urine collected 12 h prior to and over a 0–24 h period post-supplementation was analysed by UHPLC-HRMS. Sixteen flavanone metabolites and thirty-nine colon-derived phenolic catabolites were identified and quantified. The major compounds were hesperetin-3′-glucuronide, along with hippuric acids and the C 6 –C 3 phenolic acids 3-(3 ′ -hydroxy-4′-methoxyphenyl)hydracrylic acid and 3-(4′-hydroxy-3′-methoxyphenyl)propanoic acid. A marked reduction in the 0–24 h excretion of flavanone metabolites from 29.7 μmol (9.3% recovery) to 9.3 μmol (2.9% recovery), occurred following consumption of OB-6 compared to OJ. This appeared not to be an effect of fiber on the rate of transport in the upper gut. After consumption of OJ there was a 163 ± 15 μmol excretion of colon-derived phenolic catabolites, equivalent to 43% of (poly)phenol intake and following OB-6 intake there was a further significant 30% increase. The β-oat bran in OB-6 contained 5.8 μmol of free and 52 μmol of bound phenolic derivatives compared to 371 μmol of OJ (poly)phenols. The elevated excretion of phenolics after OB-6 consumption appears not to be due to bound phenolics in the bran, rather it is consequence, principally, of a bran-mediated increase in the quantities of flavanones passing from the upper to the lower bowel where they were subjected to microbiota-mediated catabolism. This trial was registered at clinicaltrials.gov as NCT04867655. [Display omitted] • β-glucan reduces urinary excretion of orange juice flavanone metabolites. • β-glucan increase urinary excretion of phenolic colonic catabolites. • The level of endogenous hippuric acid derived from surplus amino acids is high. • Hippuric acid derived from dietary flavanone breakdown is comparatively low. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship between day-1 urine cadmium excretion and 30-day mortality in patients with acute myocardial infarction (AMI) at two centers. A total of 286 patients (222 males and 64 females) with AMI from Huashan Hospital, Shanghai and Chang Gung Memorial Hospital, Taiwan were enrolled. Basic vital signs, history, laboratory results, and day-1 urine excretion of cadmium (D1UECd) were recorded. Disease severity was assessed during the first hospitalization using Killip score, APACHE II score, and SOFA score. The main endpoint was 30-day mortality. Among the 286 patients, 218 were from Chung Gung Memorial Hospital and 68 were from Huashan Hospital with an average age of 64.2 years. Forty (14%) patients died within 30 days after AMI. The average 24-h urine cadmium level among the Chung Gung Memorial Hospital cohort was 1.5 ± 2.4 μg compared to 1.7 ± 1.7 μg among Huashan Hospital cohort, both higher than the local populations. A higher D1UECd level was significantly associated with a greater risk of 30-day mortality (odds ratio 1.68, 95% confidence interval 1.30–2.16) after controlling for a number of covariates. The ability of D1UECd to discriminate 30-day mortality was excellent, with a very high area under the curve (87.2%, 95% CI 82.0–92.5%). D1UECd was positively correlated and an independent predictor of 30-day mortality in the enrolled AMI patients. D1UECd may be a simple, objective prognostic scoring system in AMI patients. • Day-1 urine excretion of cadmium is positively correlated and an independent predictor of 30-day mortality in the enrolled AMI patients. • The prognosis predictive value of Day-1 urine excretion of cadmium is better than Killip, APACHE II and SOFA. [ABSTRACT FROM AUTHOR]

Boric acid is a vital micronutrient in animals; however, excess amounts are toxic to them. Little is known about wholebody boric acid homeostasis in animals. Seawater (SW) contains 0.4 mM boric acid, and since marine fish drink SW, their urinary system was used here as a model of the boric acid excretion system. We determined that the bladder urine of a euryhaline pufferfish (river pufferfish, Takifugu obscurus) acclimated to fresh water and SW contained 0.020 and 19 mM of boric acid, respectively (a 950-fold difference), indicating the presence of a powerful excretory renal system for boric acid. Slc4a11 is a potential animal homolog of the plant boron transporter BOR1; however, mammalian Slc4a11 mediates H+ (OH-) conductance but does not transport boric acid. We found that renal expression of the pufferfish paralog of Slc4a11, Slc4a11A, was markedly induced after transfer from fresh water to SW, and Slc4a11A was localized to the apical membrane of kidney tubules. When pufferfish Slc4a11A was expressed in Xenopus oocytes, exposure to media containing boric acid and a voltage clamp elicited whole-cell outward currents, a marked increase in pHi, and increased boron content. In addition, the activity of Slc4a11A was independent of extracellular Na+. These results indicate that pufferfish Slc4a11A is an electrogenic boric acid transporter that functions as a B(OH)4- uniporter, B(OH)3-OH- cotransporter, or B(OH)3/H+ exchanger. These observations suggest that Slc4a11A is involved in the kidney tubular secretion of boric acid in SW fish, probably induced by the negative membrane potential and low pH of urine. [ABSTRACT FROM AUTHOR]

Background Low 24-h urinary potassium excretion, reflecting low potassium intake, is associated with premature mortality in the general population. Objectives To determine whether urinary potassium excretion is associated with all-cause mortality in patients with type 2 diabetes. Methods We performed a prospective cohort study in 654 patients with type 2 diabetes in the Diabetes and Lifestyle Cohort Twente (DIALECT). Sex-specific tertiles of 24-h urinary potassium excretion were analyzed in a multivariable Cox regression model with all-cause mortality. The outpatient program of the hospital uses a continuous surveillance system by the municipal registry of death to ensure up-to-date information on the patient's status (alive or deceased). FFQs were used to study associations between urinary potassium excretion and food products. Results Urinary potassium excretion at baseline was 84 ± 25 mmol/d in males and 65 ± 22 mmol/d in females, corresponding to estimated potassium intakes of 4250 ± 1270 mg/d and 3300 ± 875 mg/d. During a median follow-up of 5.2 (IQR: 2.7−7.9] y, 96 participants died. In a fully adjusted model, patients in the lowest sex-specific tertile had a higher risk of all-cause mortality, compared with patients in the highest sex-specific tertile (HR: 2.09; 95% CI: 1.06, 4.10; P  = 0.03). Patients in the lowest sex-specific tertile consumed fewer fruits and vegetables, dairy, coffee, and potato products compared with patients in the highest sex-specific tertile (all P  < 0.05). Conclusions Low potassium intake is associated with a higher risk of all-cause mortality in Dutch patients with type 2 diabetes. Intervention studies are needed to determine whether potassium supplementation improves longevity in patients with type 2 diabetes. This trial was registered in the Dutch Trial Register as NTR trial code 5855. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of 2 over-the-counter alkalizing agents on 24 hour urinary parameters.Materials and Methods: Ten healthy volunteers without a history of kidney stones were recruited to complete a baseline 24 hour urinalysis with a 4 day diet inventory. Participants then maintained the same diet on either LithoLyte (20 mEq 2 times per day) or KSPtabs (1 tablet 2 times per day) and submitted another 24 hour urinalysis. The process was repeated with the other supplement. Urinary alkali parameters were compared to baseline, and side effects were elicited with a questionnaire.Results: LithoLyte intake resulted in a non-significant increase in citrate (597-758 mg/day, P =.058, an increase in urine pH (6.46-6.66, P =.028), and a decrease in urine ammonium (41-36 mmol/day, P =.005) compared to baseline. KSPtabs resulted in an increase in citrate (597-797 mg/day, P =.037) and urine pH (6.46-6.86, P =.037), with a non-significant decrease in ammonium (41-34 mmol/day, P =.059). No significant differences were seen comparing urinary analytes between LithoLyte and KSPtabs. With Litholyte, no side effects, mild, moderate, and severe side effects were seen in 50%, 40%, 10%, and 0%, respectively. With KSPtabs, rates were 60%, 20%, 10%, and 10%, respectively.Conclusion: In healthy participants without a history of kidney stones, LithoLyte and KSPtabs are effective over-the-counter alkali supplements, with a similar side effect profile to prescription potassium citrate. [ABSTRACT FROM AUTHOR]

The relationship between sodium intake and cardiovascular (CV) events remains unconfirmed. Therefore, we carried out a systematic review and dose-response meta-analysis for evaluating the potential impact of 24-hour sodium excretion on CV risk. Besides, 24-hour sodium excretion was used to replace daily sodium diet intake. We searched ISI Web of Science, Embase, PubMed, and the Cochrane Library. Our study included cohort studies reporting hazard ratio (HR). The random-effects model was used for summarizing the total relative risks (RR s) between the included studies. In addition, the generalized least-squares regression was employed to fit the study model. A total of 9 studies involving 645,006 participants were included in this study. A significant non-linear relationship was observed between sodium excretion and CV events (P non-linearity < 0.001). In studies collecting 24-h urine samples, the sodium excretion and CV events risk were associated linearly (RR : 1.04; 95% CI : 1.01, 1.07). In a linear dose-response manner, every 1 g increase in sodium intake was associated with an increased risk of CV events up to 4%. Further studies are required to validate our conclusions further. [ABSTRACT FROM AUTHOR]

Pinocembrin-7-O-β-D-glucoside (PCBG) isolated from Penthorum chinense Pursh was proven to display a wide range of pharmacological effects including hepatoprotection, anti-hepatoma and antifungal activities, etc. The research aims to qualitatively analyze the metabolites of PCBG in rat plasma, urine, bile and feces, and further perform the excretion study of PCBG and its major metabolite pinocembrin (PCB). Fifteen rats were divided into three groups (n=5 for each group) for blood, bile, urine and feces collection, respectively. After PCBG suspension was intragastrically administered to rats at 50 mg/kg, biological samples were collected and processed. The metabolites in each matrix were detected by UHPLC-Q-Exactive-MS/MS. A total of 111 metabolites were observed in plasma, urine, bile and feces, which include hydroxylated, sulfated and glucuronized metabolites, etc. In addition, an UHPLC-MS/MS method was established and applied for the excretion quantification of PCBG and PCB in rat urine, bile, and feces samples. Studies on excretion have shown that PCBG is mainly excreted through feces. The cumulative excretion rates of PCBG and PCB in rat urine, bile and feces were (4.5±2.4)%, (0.2±0.1)% and (18.4±10.5)%, respectively. After hydrolysis by β-glucuronidase/sulfatase, the excretion rates of PCB in urine and bile were (5.7±2.8)% and (8.9±4.2)%. This study contributes to preclinical research on PCBG and explains its pharmacological effects. • 111 metabolites of PCBG were observed in plasma, urine, bile and feces. • An UPLC-MS/MS method was applied to determine the contents of PCBG and PCB in rat samples. • This study contributes to preclinical research on PCBG. [ABSTRACT FROM AUTHOR]

• In mice, luteinizing hormone (LH) treatment significantly increased urinary calcium excretion and induced a secondary increase in serum parathyroid hormone. • In healthy men, human-chorionic-gonadotropin (hCG) injections led to a significant increase in urinary calcium excretion, and increase in serum PTH levels, and calcitriol (1,25 (OH) 2 D 3). • The common receptor for LH and hCG, LHCGR, is expressed in human kidney tissue. • LHCGR may be influencing calcium homeostasis directly or indirectly. Animal and human studies have suggested that sex steroids have calciotropic actions, and it has been proposed that follicle-stimulating hormone (FSH) may exert direct effects on bone. Here, we demonstrate the expression of the receptor for Luteinizing hormone (LH) and human choriogonadotropin (hCG), LHCGR, in human kidney tissue, suggesting a potential influence on calcium homeostasis. To investigate the role of LHCGR agonist on calcium homeostasis in vivo , we conducted studies in male mice and human subjects. Male mice were treated with luteinizing hormone (LH), and human extrapolation was achieved by injecting 5000 IU hCG once to healthy men or men with hypergonadotropic or hypogonadotropic hypogonadism. In mice, LH treatment significantly increased urinary calcium excretion and induced a secondary increase in serum parathyroid hormone (PTH). Similarly, hCG treatment in healthy men led to a significant increase in urinary calcium excretion, serum PTH levels, and 1,25 (OH) 2 D 3 , while calcitonin, and albumin levels were reduced, possibly to avoid development of persistent hypocalcemia. Still, the rapid initial decline in ionized calcium coincided with a significant prolongation of the cardiac QTc-interval that normalized over time. The observed effects may be attributed to LH/hCG-receptor (LHCGR) activation, considering the presence of LHCGR expression in human kidney tissue, and the increase in sex steroids occurred several hours after the changes in calcium homeostasis. Our translational study shed light on the intricate relationship between gonadotropins, sex hormones and calcium, suggesting that LHCGR may be influencing calcium homeostasis directly or indirectly. [Display omitted] [ABSTRACT FROM AUTHOR]

Multidrug and toxin extrusion (MATE) family transporters excrete toxic compounds coupled to Na+/H+ influx. Although structures of MATE transporters are available, the mechanism by which substrate export is coupled to ion influx remains unknown. To address this issue, we conducted a structural analysis of Pyrococcus furiosus MATE (PfMATE) using solution nuclear magnetic resonance (NMR). The NMR analysis, along with thorough substitutions of all non-exposed acidic residues, confirmed that PfMATE is under an equilibrium between inward-facing (IF) and outward-facing (OF) conformations, dictated by the Glu163 protonation. Importantly, we found that only the IF conformation exhibits a mid-μM affinity for substrate recognition. In contrast, the OF conformation exhibited only weak mM substrate affinity, suitable for releasing substrate to the extracellular side. These results indicate that PfMATE is an affinity-directed H+ antiporter where substrates selectively bind to the protonated IF conformation in the equilibrium, and subsequent proton release mechanistically ensures H+-coupled substrate excretion by the transporter. [Display omitted] • The substrate/H+-antiport mechanism of PfMATE was structurally analyzed by solution NMR • The equilibrium between the IF/OF conformations is dictated by Glu163 protonation • Only the IF conformation has a sufficient affinity for substrate binding • The affinity-directed transport mechanism ensures H+-coupled substrate excretion Takeuchi et al. structurally characterized the substrate/H+-antiport mechanism of the multidrug transporter PfMATE. PfMATE is an affinity-directed H+ antiporter and substrates selectively bind to its protonated IF conformation. Subsequent proton release is coupled to a structural rearrangement to the OF conformation, which mechanistically ensures H+-coupled substrate excretion. [ABSTRACT FROM AUTHOR]

Migratory wild birds can carry various pathogens, such as influenza A virus, which can spread to globally and cause disease outbreaks and epidemics. Continuous epidemiological surveillance of migratory wild birds is of great significance for the early warning, prevention, and control of epidemics. To investigate the pathogen infection status of migratory wild birds in eastern China, fecal samples were collected from wetlands to conduct pathogen surveillance. The results showed that duck orthoreovirus (DRV) and goose parvovirus (GPV) nucleic acid were detected positive in the fecal samples collected from wild ducks, egrets, and swan. Phylogenetic analysis of the amplified viral genes reveals that the isolates were closely related to the prevalent strains in the regions involved in East Asian-Australasian (EAA) migratory flyway. Phylogenetic analysis of the amplified viral genes confirmed that they were closely related to circulating strains in the regions involved in the EAA migration pathway. The findings of this study have expanded the host range of the orthoreovirus and parvovirus, and revealed possible virus transmission between wild migratory birds and poultry. [ABSTRACT FROM AUTHOR]

Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6+0 to 13+6, 14+0 to 27+6, and 28+0 to 41+6 weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (≥35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6–100.0) vs 70.5 (50.5–100.0) mg, 85.8 (62.0–117.0) vs 96.0 (68.0–127.8) mg, and 106.6 (76.0–146.2) vs 114.7 (81.5–153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management. [Display omitted] [ABSTRACT FROM AUTHOR]

Narrow spectrum nano-antibiotics are supposedly the future trouble-shooters to improve the efficacy of conventional antimicrobials for treatment of severe bacterial infections, remove contamination from water and diminish the development of antibiotic resistance. In this study, antimicrobial peptide functionalized boron-carbon-nitride nanosheets ((Ant)pep@BCN NSs) are developed that are a promising wastewater disinfector and antibiotic resistant bactericide agent. These nanosheets are developed for selective removal and effective inactivation of antibiotic resistant bacteria (ARB) from water in presence of two virulent bacteria. The (Ant)pep@BCN NSs provide reactive surface receptors specific to the ARB. They mimic muralytic enzymes to damage the cell membrane of ARB. These NSs demonstrate 3-fold higher antimicrobial efficiency against the targeted ARB compared to pristine BCN even at lower concentrations. To the best of our knowledge, this is the first time that functionalized BCN has been developed to remove ARB selectively from wastewater. Furthermore, the (Ant)pep@BCN selectively reduced the microbiological load and led to morphological changes in Gram negative ARB in a mixed bacterial inoculum. These ARBs excreted outer–inner membrane vesicles (OIMVs) of triangular shape as a stimuli response to (Ant)pep@BCN NSs. These novel antimicrobial peptide-NSs have potential to improve treatment efficacy against ARB infections and water contamination. [Display omitted] • The synthesized (Ant)pep@BCN nanosheets act as narrow spectrum nano-antibiotic. • (Ant)pep@BCN NSs targets ARB in a pool of similar kinds of bacteria. • (Ant)pep@BCN NSs show muralytic activity. • (Ant)pep@BCN targets the parental peptide linkages on ARB leading selectivity. • The ARB's stimuli-response consists of excretion of triangular nanostructures. [ABSTRACT FROM AUTHOR]

Future food systems aim to achieve improved resource use efficiency and minimized environmental footprint through a circular bioeconomy-based approach. Aquaponics is a hallmark of such circular food production. The image of a circular nutrient utilization efficiency in aquaponics is often weakened by the daily use of additional inorganic fertilizers in such systems. As circular bioeconomy greatly emphasizes developing bio-based solutions, the presented novel inventory 'TilaFeed' and its associated utility tools is a step towards achieving more circular nutrient utilization and bioeconomy in future aquaponics. Through the formulation of tailored fish feed that is compatible with aquaponic systems' needs (e.g. plant nutrient requirement, mineralization efficiency of microbial sludge digesters), the objectives of TilaFeed are (i) to solve nutrient constraints in aquaponic systems, both for fish and plants; (ii) to avoid or strongly limit artificial fertilizer use in aquaponics by smartly tailored aquafeeds; and (iii) to equip system managers with decision-making tools for improved nutrient planning of their aquaponic systems. TilaFeed is a bio-based inventory. It integrates material (nutrient) flow information from feed to fish (in-vivo nutrient partitioning, forms of excretion) to environment (in-situ nutrient loading, nutrient forms) and primary producers (mineralization by microbes, available nutrients to plants). Based on TilaFeed-Model, feed for future aquaponics may be more precisely formulated with the principle that nutrients are not only a resource for fish, but excreted nutrients from fish (feed) also fertilize the microbes and plants. • Presented inventory may aid in centralized and 'one formula' solutions for aquaponics. • Avoid or limit artificial fertilizer use in aquaponics by smartly tailored aquafeeds. • Equip system managers with improved nutrient management of their aquaponic systems. • Compatible with nutrient formulation software using linear or stochastic programming. [ABSTRACT FROM AUTHOR]

d - α -Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development. This study reported an analysis of the in vivo fate of D- α -tocopheryl polyethylene glycol 1000 succinate (TPGS) and its metabolite PEG1000 in rat using an innovative bioassay based on an in-source collision-induced dissociation strategy in liquid chromatography–tandem mass spectrometry. [Display omitted] [ABSTRACT FROM AUTHOR]

The bioavailability of apigenin and its O -glycosides in humans was investigated with apigenin-4′-glucuronide (Ap-4′-GlcUA), apigenin-7-glucuronide and apigenin-7-sulfate being identified as in vivo metabolites. Apigenin per se was poorly absorbed with metabolites equivalent to 0.5% of intake excreted in urine 0–24 h post-intake. Consumption of a parsley drink containing apigenin-7- O -(2″- O -apiosyl)glucoside resulted in the peak plasma concentration (C max) of Ap-4′-GlcUA occurring after 4 h, indicative of absorption in the lower gastrointestinal tract (GIT). Urinary excretion of the three metabolites corresponded to 11.2% of intake. Ingestion of dried powdered parsley leaves with yogurt extended the C max of Ap-4′-GlcUA to 6 h. Consumption of chamomile tea containing apigenin-7′- O -glucoside resulted in a 2 h C max of Ap-4′-GlcUA, in keeping with absorption in the upper GIT. Urinary excretion was equivalent to 34% of intake. Intake of the parsley drink provided information on intra- and inter-individual variations in the level of excretion of the apigenin metabolites. This trail was registered at clinicaltrials.gov as NCT03526081. [Display omitted] • Human absorption and metabolism of apigenin and its glycosides. • Identification of apigenin metabolites in plasma and urine. • Plasma pharmacokinetics and urinary excretion of apigenin metabolites. • Impact of sugar moiety on apigenin absorption. • Essential data for ex vivo tissue studies using apigenin metabolites. [ABSTRACT FROM AUTHOR]

Environmental degradation has been attributed to inefficient nitrogen utilization from pastoral dairy production systems. This degradation has especially been associated with the urine patch, which has been identified as a key component of nitrate leaching to waterways. However, a lack of information exists regarding the pattern of urination events and individual urination characteristics across the day, which would help inform strategic management decisions. The aim of this study was therefore to evaluate and report the patterns and characteristics of fecal and urination events throughout the day for cows divergent for milk urea nitrogen breeding values (MUNBV) on either a plantain [ Plantago lanceolata L. (PL)] or ryegrass [ Lolium perenne L. (RG)] diet as ways to reduce environmental impact. Sixteen multiparous lactating Holstein Friesian × Jersey cows divergent for MUNBV were housed in metabolism crates for 72 h, with all excretion events captured and analyzed. Cows selected as low for MUNBV consistently had a 65.2-kg lower urinary urea nitrogen (UUN) load (kg/ha) than high MUNBV cows for all hours of the day when consuming RG. The association between lower urinary urea loading rates and less N leaching implies a reduced environmental impact from low MUNBV cows consuming RG. When cows consumed PL, regardless of MUNBV, they had on average a 137.5-kg (UUN/ha) lower loading rate compared with high MUNBV cows on RG and a 72.2-kg (UUN/ha) lower loading rate compared with low MUNBV cows consuming RG across the day. Cows on PL also exhibited a different diel pattern of UUN load compared with cows consuming RG. Differences in the diel pattern of N excreted in feces were also detected based on MUNBV and by diet, with low MUNBV cows excreting on average 3.06 g more N in feces per event for the majority of the day compared with high MUNBV cows when consuming RG. Lower UUN loading rates and more N excreted in feces indicate a potentially lower environmental impact from low MUNBV cows when consuming RG compared with high MUNBV cows. The use of the PL diet also resulted in lower UUN loading rates and greater levels of N excreted in feces compared with RG, therefore also indicating its ability to reduce environmental impact compared with RG. [ABSTRACT FROM AUTHOR]

Prerenal acute kidney injury (prerenal AKI), hepatorenal syndrome (HRS–AKI), and acute tubular necrosis (ATN–AKI) are the various phenotypes of acute kidney injury, which are described in decompensated cirrhosis. It has therapeutic and prognostic implications. We aimed to evaluate the diagnostic utility of fractional excretion of sodium and urea (FENa and FEUrea) for differentiating AKI phenotypes. A prospective analysis was performed in 200 patients with decompensated cirrhosis with AKI to derive receiver operating curve, optimal cut-off, sensitivity, and specificity. These findings were validated in an independent cohort (n = 50) to differentiate ATN–AKI, HRS–AKI, and prerenal AKI. The incidence of prerenal AKI, HRS–AKI, and ATN–AKI were 37.5%, 34%, and 28.5% in the derivation cohort and 28%, 38%, and 34% in the validation cohort respectively. The median FENa was significantly different in various phenotypes of AKI in the derivation and validation cohort (P 0.001); FEUrea was significantly different in the derivation cohort (P 0.0001), not in the validation cohort (P 0.106). The AUC for FENa (cut-off, sensitivity/specificity) was 86.6% (0.567, 89/71) and for FEUrea was 60.3% (34.73, 70/58) for ATN–AKI vs. non-ATN–AKI. The area under the curve for FENa to differentiate between HRS–AKI vs. non-HRS–AKI was 74.5%. FEUrea could not differentiate HRS-AKI vs. non-HRS–AKI (AUC 60.4%) satisfactorily. FENa and FEUrea were unable to differentiate between prerenal AKI and HRS-AKI (AUC <70%). Among cirrhotics FENa at admission is a simple, commonly available clinical tool that can be used to differentiate structural AKI from prerenal AKI and HRS–AKI. The newly derived lowered cut-off value of FENa makes the diagnosis of ATN-AKI easier, faster and thus obviates the need for extensive workup in a significant proportion of patients. FENa appears better than FEUrea in decompensated cirrhosis with AKI. [ABSTRACT FROM AUTHOR]

Vanadium is a ubiquitous environmental contaminant although there are limited data to assess potential adverse human health impact following oral exposure. In support of studies investigating the subchronic toxicity of vanadyl sulfate (V4+) and sodium metavanadate (V5+) following perinatal exposure via drinking water in male and female rats, we have determined the internal exposure and urinary excretion of total vanadium at the end of study. Water consumption decreased with increasing exposure concentration following exposure to both compounds. Plasma and urine vanadium concentration normalized to total vanadium consumed per day increased with the exposure concentration of vanadyl sulfate and sodium metavanadate suggesting absorption increased as the exposure concentration increased. Additionally, females had higher concentrations than males (in plasma only for vanadyl sulfate exposure). Animals exposed to sodium metavanadate had up to 3-fold higher vanadium concentration in plasma and urine compared to vanadyl sulfate exposed animals, when normalized to total vanadium consumed per day, demonstrating differential absorption, distribution, metabolism, and excretion properties between V5+ and V4+ compounds. These data will aid in the interpretation of animal toxicity data of V4+ and V5+ compounds and determine the relevance of animal toxicity findings to human exposures. • Vanadium (V) is a ubiquitous environmental contaminant. • Internal exposure was determined in rodents after oral exposure to V4+ and V5+. • Plasma and urine V levels increased more than proportional to V4+ and V5+ dose. • Exposure to V5+ caused up to 3-fold higher plasma and urine V levels than V4+. • Data demonstrate differential ADME properties between V5+ and V4+ compounds. [ABSTRACT FROM AUTHOR]

The development of safe and efficient dietary selenium sources to promote lead excretion is of great importance for public health. In this research, proteins from original Pleurotus eryngii (PEP) and Se-enriched P. eryngii (SePEP, Se content: 360.64 ± 3.11 mg/kg) were extracted and purified respectively for the further comparison of structural and digestive characteristics. Caco-2 monolayer membrane, in vitro simulated fermentation and acute lead exposure mice model were constructed to evaluate the effects of PEP and SePEP on lead excretion. The results indicated that Se biofortification significantly altered the amino acid composition and reduced the total sulfhydryl content of proteins (p < 0.05). SePEP could better alleviate lead-induced intestinal barrier damage and inhibit the absorption and accumulation of lead in both cell and mice models. Furthermore, SePEP promoted fecal adsorption and excretion of lead via regulating gut microbiota composition. SePEP can be considered a potentially functional Se source to promote lead excretion. [Display omitted] • Se biofortification significantly altered the Pleurotus eryngii protein structure. • SePEP alleviated Pb-induced intestinal barrier damage and inflammatory. • SePEP inhibited absorption and accumulation of Pb in both cell and mice models. • SePEP regulated gut microbiota composition and promoted the fecal excretion of Pb. [ABSTRACT FROM AUTHOR]

• Granule-based anammox reactor achieves a stable and high NLR with folate dosage. • Folate dosage leads to the granular floatation potential decreasing by 67.1%. • EPS decline and surface pore plugging dredge contribute to floatation control. • Anammox bacteria reduce EPS secretion due to attenuated cross-feeding after adding folate. Although granular floatation has been recognized as a significant issue hindering the application of high-rate anammox biotechnology, limited knowledge is available about its causes and control strategies. This study proposed a novel control strategy by adding folate, and demonstrated its role in the granular floatation alleviation through long-term operation and granular characterizations. It was found that the floatation of anammox granular sludge was obviously relieved with the decreased sludge floatation potential by 67.1% after dosing with folate (8 mg/L) at a high nitrogen loading rate of 12.3 kg-N/(m3·d). Physiochemical analyses showed that the decrease of extracellular polymeric substances (EPS) content (mainly protein), the alleviation of granular surface pore plugging in conjunction with the smooth discharge of generated nitrogen gas were collectively responsible for efficient floatation control. Moreover, metagenomic analysis suggested that the synergistic interactions between anammox bacteria and their symbionts were attenuated after dosing exogenous folate. Anammox bacteria would reduce their synergistic dependence on the symbionts, and decline the supply of metabolites (e.g., amino acids and carbohydrates in EPS) to symbiotic bacteria. The declined EPS excretion contributed to the alleviation of granular floatation by dredging pores blockage, thus leading to a stable system performance. The findings not only offer insights into the role of microbial interaction in granular sludge floatation, but also provide a feasible approach for controlling the floatation issue in anammox granular-based processes. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Chronic consumption of orange juice resulted in significant change in the metabolism of citrus flavanones; • A high inter-individual variability in the excreted flavanone metabolites decreases after chronic consumption; • Transient changes in gut microbiota was observed with decrease in the relative abundance of Blautia; • There is a significant decrease in mirobial β-glucosidase activity. The metabolism and absorption of citrus flavanones are intrinsically linked to the gut microbiota, creating a bidirectional relationship where these compounds influence the microbiome, and in turn, the microbiota affects their metabolism. This study evaluates the effect of acute and chronic consumption of orange juice (OJ) on the urinary excretion of gut-derived flavanone metabolites and the gut microbiota. Health volunteers ingested 500 mL of OJ for 60 days in a single-arm human intervention study. Blood and feces were collected at baseline and after 60 days, with an additional 24-hour urine collection after a single dose on day 1 and day 63. LC-MS/MS analyzed urinary flavanone metabolites, while 16S rRNA sequencing characterized gut microbiota. Total urinary hesperetin conjugates excretion significantly decreased over 60 days, while gut-derived total phenolic acids, particularly three hydroxybenzoic acids, increased. Moreover, the heterogeneity of the total amount of flavanone conjugates, initially categorizing individuals into high-, medium- and low- urinary excretor profiles, shifted towards medium-excretor, except for five individuals who remained as low-excretors. This alteration was accompanied by a decrease in intestinal β-glucosidase activity and a shift in the relative abundance of specific genera, such as decreases in Blautia , Eubacterium hallii , Anaerostipes , and Fusicatenibacter , among which, Blautia was associated with higher urinary flavanone conjugates excretion. Conversely, an increase in Prevotella was observed. In summary, chronic OJ consumption induced transient changes in gut microbiota and altered the metabolism of citrus flavanones, leading to distinct urinary excretion profiles of flavanone metabolites. [ABSTRACT FROM AUTHOR]

Pharmacokinetic studies are pivotal in drug development, focusing on absorption, distribution, and excretion of active compounds. Effective sample preparation methods play a crucial role in these studies. Traditional techniques like protein precipitation and liquid-liquid extraction often involve toxic solvents and are time-consuming. Recently, deep eutectic solvent (DES) has emerged as an eco-friendly alternative due to its high efficiency, low cost, and low toxicity. This study introduces a novel sample pretreatment method using CO 2 -switchable DES in liquid-liquid microextraction (LLME) to enhance speed, accuracy, and sensitivity in complex biological samples analysis. A liquid-liquid microextraction sample pretreatment method based on switchable DES combined with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the analysis of urine and tissue samples. The method was optimized through systematic investigation of key parameters, including DES type, volume, molar ratio, pH, vortex time, gas purge time, and salt addition. The resulting procedure exhibited satisfying linearity (r2 ≥ 0.9958), good precision (RSD ≤6.01 %), desirable recovery (52.44%–98.12 %) and matrix effect (86.22%–119.30 %), and the accuracy and precision of stability were within the ±15 % limit. The proven methods were further applied to urinary excretion study and tissue distribution study of Nelumbinis plumula (NP) extract. The results indicated that the total cumulative excretion of liensinine, isoliensinine and neferine in urine within 240 h was 4.96 %, 0.66 % and 0.44 %, respectively. The tissue distribution study showed that alkaloids mainly distribute in liver, kidney, and spleen. This research introduces a groundbreaking technique distinguished by its simplicity, speed, cost-effectiveness, and environmental friendliness. This approach, utilizing CO 2 -switchable DES as an extraction solvent for LLME, integrates deproteinization and removal of interfering molecules into a single step. This integration showcases its efficiency and convenience, demonstrating significant promise for various applications in the analysis of biological samples. Additionally, this study provides the first report on urinary excretion and tissue distribution of alkaloids from NP using a DES-LLME method. These findings offer valuable insights into the in vivo behavior of herbal medicine, enhancing understanding of pharmacological actions and facilitating clinical rational administration. CO 2 -switchable deep eutectic solvent based liquid–liquid microextraction method was developed and applied to the urinary excretion study and tissue distribution study of alkaloids in rats after oral administration of NP extract. [Display omitted] • CO 2 -switchable DES composed of monoethanolamine and 4-methoxyphenol was used as extraction solvent. • Switchable DES-LLME method integrates deproteinization and removal of interfering molecules into a single step. • HPLC-MS/MS system was used for simultaneous quantification of the three alkaloids in urine and tissue samples. [ABSTRACT FROM AUTHOR]

The excretory mechanisms of stenohaline marine osmoconforming crabs are often compared to those of the more extensively characterized euryhaline osmoregulating crabs. These comparisons may have limitations, given that unlike euryhaline brachyurans the gills of stenohaline marine osmoconformers possess ion-leaky paracellular pathways and lack the capacity to undergo ultrastructural changes that can promote ion-transport processes in dilute media. Furthermore, the antennal glands of stenohaline marine osmoconformers are poorly characterized making it difficult to determine what role urinary processes play in excretion. In the presented study, ammonia excretory processes as well as related acid-base equivalent transport rates and mechanisms were investigated in the Dungeness crab, Metacarcinus magister – an economically valuable stenohaline marine osmoconforming crab. Isolated and perfused gills were found to predominantly eliminate ammonia through a microtubule network-dependent active NH 4 + transport mechanism that is likely performed by cells lining the arterial pockets of the gill lamella where critical Na+/K+-ATPase detection was observed. The V-type H+-ATPase – a vital component to transbranchial ammonia excretion mechanisms of euryhaline crabs - was not found to contribute significantly to ammonia excretion; however, this may be due to the transporter's unexpected apical localization. Although unconnected to ammonia excretion rates, a membrane-bound isoform of carbonic anhydrase was localized to the apical and basolateral membranes of lamella suited for respiration. Urine was found to contain significantly less ammonia as well as carbonate species than the hemolymph, indicating that unlike those of some euryhaline crabs the antennal glands of the Dungeness crab reabsorb these molecules rather than eliminate them for excretion. [Display omitted] • Most ammonia is actively excreted by the Dungeness crab gills, likely in lamellar pockets • Active ammonia excretion depends on NKA activity and the microtubule network. • Branchial V-type H+-ATPase is localized to the apical and cytosolic vesicular membranes • Apical and basolateral membranes of the gill express membrane-bound carbonic anhydrase • Antennal glands reabsorb inorganic carbon and ammonia rather than excrete wastes [ABSTRACT FROM AUTHOR]

In this study the efficacy of an intramuscular formulation of toltrazuril combined with gleptoferron for the control of porcine cystoisosporosis caused by Cystoisospora suis was investigated. The study was carried out on three Belgian farms with a confirmed history of C. suis infections. As none of the farms implemented a standardized toltrazuril treatment regimen for their piglets, the presence of resistant C. suis strains seems improbable. In total 90 litters, representing 1249 piglets, were included in the study and randomly allocated to either the treatment or control group. Piglets in the treatment group received a single intramuscular injection, containing 45 mg toltrazuril and 200 mg gleptoferron, between 1 and 3 days of age. Piglets in the control group received a single injection with only 200 mg gleptoferron. The effect of treatment on oocyst excretion, expressed in oocysts per gram of feces (OPG), average daily weight gain (ADG) and mortality was determined both pre- and post-weaning. A significant decrease in OPG as well as a decrease in the number of litters (pre-weaning) and pens (post-weaning) that tested positive for cystoisosporosis, was observed in the treated animals compared to the controls. Furthermore, treatment resulted in an increased ADG during the period from day 1 to day 21 (p-value: 0.03881). There was no significant difference in mortality observed between the treatment group to the control group (p-value: 0.2167). To our knowledge, this is the first report on the effect of toltrazuril on oocyst excretion after weaning. This finding highlights the potential long-term benefits of the treatment beyond the initial administration. • Toltrazuril-gleptoferron reduces Cystoisospora suis excretion pre- and post-weaning. • Toltrazuril-gleptoferron significantly increases pre-weaning weight gain. • First report on the effect of toltrazuril on oocyst excretion post-weaning. [ABSTRACT FROM AUTHOR]

Linaprazan (AZD0865, TX07) is one of potassium-competitive acid blockers. However, linaprazan is rapidly excreted from the body, shortening its acid inhibition property. Linaprazan glurate (X842) is a prodrug of linaprazan with a prolonged inhibitory effect on gastric acid secretion. Linaprazan glurate has entered clinical trials, but few studies have reported its metabolism in non-clinical and clinical settings. In this study, we studied the pharmacokinetics, tissue distribution, mass balance, and metabolism of linaprazan glurate in rats after a single oral dose of 2.4 mg/kg (100 µCi/kg) [14C]linaprazan glurate. The results demonstrated that linaprazan glurate was mainly excreted via feces in rats with 70.48% of the dose over 168 h. The plasma AUC 0 – ∞ of linaprazan glurate in female rats was 2 times higher than that in male rats. Drug-related substances were mainly concentrated in the stomach, eyes, liver, small intestine, and large intestine after administration. In blood, drug-related substances were mostly distributed into plasma instead of hemocytes. In total, 13 metabolites were detected in rat plasma, urine, feces, and bile. M150 (2,6-dimethylbenzoic acid) was the predominant metabolite in plasma, accounting for 80.65% and 67.65% of AUC 0–24 h in male and female rats, respectively. Based on the structures, linaprazan glurate was mainly hydrolyzed into linaprazan, followed by a series of oxidation, dehydrogenation, and glucuronidation in rats. Besides, CES2 is the main metabolic enzyme involved in the hydrolysis of linaprazan glurate to linaprazan. • The ADME of linaprazan glurate in rats were studied by radio-labeling technology. • The metabolic pathways of linaprazan glurate in rats were revealed. • The carboxylesterase isoenzymes involved in the generation of linaprazan (active metabolite) were identified. [ABSTRACT FROM AUTHOR]

Aluminum (Al) adjuvants have been used in vaccines and subcutaneous immunotherapy (SCIT) for decades. Despite indisputable neurotoxic properties of Al, there is no clear evidence of a causal relationship between their use and any neurotoxic side effects. However, recent rat studies have shown an accumulation of Al from adjuvants in tissues, especially in bones. Since the human toxicokinetics of Al-adjuvants are poorly understood, this study aimed to evaluate whether up-dosed or long-term SCIT with Al-coupled extracts leads to increased Al load in humans. This observational cross-sectional case-control study explored Al excretion in hymenoptera venom allergy patients recruited in 2020 before initiation (n = 10) and during ongoing (n = 12) SCIT with Al-based preparations. Urine samples were collected before and 24 h after the SCIT injections and analyzed for aluminum content by using atomic absorption spectrometry. The cumulative administered Al dose was extracted from patient records. Patients receiving long-term immunotherapy were treated between 2.8 and 13.6 years (mean 7.1). Other potential sources of Al exposure were surveyed. Patients who had received Al-coupled immunotherapy for several years showed significantly (p < 0.001) higher Al excretion than the controls at initiation of immunotherapy (mean 18.2 μg/gC vs. 7.9 μg/gC) and predominantly (73%) were above the 95th percentile of the general populations' exposure (>15 μg/gC), however, without reaching levels of toxicological concern (>50 μg/gC). Taking both groups together excreted Al levels correlated with the cumulative administered Al dose from SCIT (linear regression: Al urine = 8.258 + 0.133*Al cum ; p = 0.001). These results suggest a relevant iatrogenic contribution of long-term SCIT to human internal Al burden and potential accumulation. Considering the medical benefits of Al-adjuvants and SCIT a differentiated risk-benefit analysis is needed. For certain scenarios of potential toxicological concern in clinical practice biomonitoring might be advisable. [Display omitted] • No short-term effects measurable from single aluminum-adjuvanted injections. • Increased aluminum excretion after multi-annual aluminum-adjuvanted immunotherapy. • Increased aluminum excretion mostly without reaching level of toxicological concern. • Excreted aluminum levels correlate with the cumulative aluminum dose from adjuvants. • Iatrogenic contribution to human aluminum burden through long-term immunotherapy. [ABSTRACT FROM AUTHOR]

To date, characterization of the first-pass effect of orally administered drugs consisting of local intestinal absorption and metabolism, portal vein transport and hepatobiliary processes remains challenging. Aim of this study was to explore the applicability of a porcine ex-vivo perfusion model to study oral absorption, gut-hepatobiliary metabolism and biliary excretion of midazolam. Slaughterhouse procured porcine en bloc organs (n = 4), were perfused via the aorta and portal vein. After 120 min of perfusion, midazolam, atenolol, antipyrine and FD4 were dosed via the duodenum and samples were taken from the systemic- and portal vein perfusate, intestinal faecal effluent and bile to determine drug and metabolite concentrations. Stable arterial and portal vein flow was obtained and viability of the perfused organs was confirmed. After intraduodenal administration, midazolam was rapidly detected in the portal vein together with 1-OH midazolam (E G-pv of 0.16±0.1) resulting from gut wall metabolism through oxidation. In the intestinal faecal effluent, 1-OH midazolam and 1-OH midazolam glucuronide (E G-intestine 0.051±0.03) was observed resulting from local gut glucuronidation. Biliary elimination of midazolam (0.04±0.01 %) and its glucuronide (0.01±0.01 %) only minimally contributed to the enterohepatic circulation. More extensive hepatic metabolism (F H 0.35±0.07) over intestinal metabolism (F G 0.78±0.11) was shown, resulting in oral bioavailability of 0.27±0.05. Ex vivo perfusion demonstrated to be a novel approach to characterize pre-systemic extraction of midazolam by measuring intestinal as well as hepatic extraction. The model can generate valuable insights into the absorption and metabolism of new drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • We explore mechanism of landfill sludge (LS) nature variations using micro-omics. • Dewaterability and fluidity of LS deteriorated and then improved over landfill time. • Functional phyla in aged RDS turn to substrates due to insufficient EPS excretion. • Curing agents favor the initial release of EPS and maintenance of microbial activity. • Aged SDS has more robust anaerobic reactions and better dewaterability than RDS. Landfill sludge (LS) with high moisture content is non-standard and insecure, necessitating the investigation of characteristic variation mechanisms to guide its further treatment. In this study, the degradation rules and property changes of raw dewatered sludge (RDS) and solidification sludge (SDS) with varying landfill ages (3–10 years) were systematically explored using physicochemical index, organic compositions, and micro-omics. The results revealed that the permeability and fluidity of LS dropped early with a high concentration of extracellular polymeric substances (EPS) from the lysis or metabolite of microorganisms. Then they rose remarkably at the post stage of the landfill when the degradation of EPS was dominant with looser sludge flocs, illustrating that fresh and aged LS required dewatering conditioners with destructive and aggregation capacity, respectively. Two-dimensional correlation spectroscopy of IR spectroscopic indicated that the hydrophilic substances in SDS were degraded antecedent to hydrophobic substances, while the opposite trend was observed in RDS, contributing to better permeability. Discrepancies between metagenomic and metaproteomic data suggested dominant functional hydrolytic bacteria and methanogens within RDS as landfill age turned to substrates due to insufficient EPS excretion, leading to sludge disintegration tendencies. While the activity of these phyla was effectively kept in SDS, resulting from that the curing agent facilitated the initial release of EPS and expedited anaerobic reaction processes, which contributed to the improved dewaterability after the long-term landfill. The results provide new insights and research strategies for comprehending the nature variation mechanisms of LS, and thus informing the technical protocol of the re-dewatering process. [ABSTRACT FROM AUTHOR]

[Display omitted] • After oral administration, ostarine is excreted in oral fluid over 8 h. • Concentrations of ostarine in oral fluid are 1 to 500 ng/ml range. • Limited concentrations will be measured after 4 h. • Soon after intake, ostarine can be transferred via kissing to the partner. • Saliva drug transfer can account for a positive anti-doping test. The presence of ostarine, a selective androgen receptor modulator (SARM) in an athlete's urine specimen constitutes one of the most frequent anti-doping rules violation as the drug is listed as a member of the S1.2 class "other anabolic agents" of the World Anti-doping Agency Prohibited List, forbidden in- and out-competition. It is possible to challenge this violation but it is at the charge of the athlete to prove innocence. The conditions to evidence no fault or negligence are mostly based on 2 points: 1. the athlete must present verified circumstances of contamination and the source of contamination must be identified; and 2. there must be verified claims by the athlete that the violation was not intentional. Some months before the Olympic games, a female athlete was suspended by a national anti-doping agency because of an adverse analytical finding for ostarine. She claimed that her violation was due to drug transfer when kissing her boyfriend, who did not inform her about his ostarine daily intake. To document this claim (excretion of ostarine in oral fluid in sufficient amounts), a male volunteer ingested 17.3 mg of ostarine (dose verified by 1H NMR). Oral fluid was collected over 8 h using the NeoSal™ collection device and was tested by liquid chromatography coupled to tandem mass spectrometry. Maximal ostarine concentration was 468 ng/mL at T + 15 min, which can also be partially attributed to mouth contamination. Ostarine was detectable during the whole period of test, with concentrations at 1–2 ng/mL after T + 4 h. These results support drug transfer during kissing and subsequent possible contamination of the partner. [ABSTRACT FROM AUTHOR]

Flonoltinib Maleate (FM) is a dual-target inhibitor that selectively suppresses Janus kinase 2/FMS-like tyrosine kinase 3 (JAK2/FLT3), which is currently in phase I/IIa clinical trial in China for the treatment of myeloproliferative neoplasms (MPNs). In this research, we used [14C]-labeled FM (14C-FM) to investigate the distribution, metabolism, and excretion of FM in rats using High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry/Radioactivity Monitoring (HPLC-HRMS/RAM) and liquid scintillation counter. The results revealed that FM displayed widespread distribution in rats. Furthermore, FM demonstrated rapid clearance without any observed risk of organ toxicity attributed to accumulation. Profiling of FM metabolites in rat plasma, feces, urine, and bile identified a total of 17 distinct metabolites, comprising 7 phase I metabolites and 10 phase II metabolites. The major metabolic reactions involved oxygenation, dealkylation, methylation, sulfation, glucuronidation and glutathione conjugation. Based on these findings, a putative metabolic pathway of FM in rats was proposed. The overall recovery rate in the excretion experiment ranged from 93.04 % to 94.74 %. The results indicated that FM undergoes extensive hepatic metabolism in SD rats, with the majority being excreted through bile as metabolites and ultimately eliminated via feces. A minor fraction of FM (<10 %) was excreted through renal excretion in the form of urine. Integration of the current results with previous pharmacokinetic investigations of FM in rats and dogs enables a comprehensive elucidation of the in vivo ADME processes and characteristics of FM, thereby establishing a solid foundation for subsequent clinical investigations of FM. [Display omitted] • Distribution, metabolism, and excretion of [14C]-Flonoltinib in rats investigated. • Wide distribution, rapid clearance, no risk of organ toxicity due to accumulation found. • 17 metabolites identified in rat plasma, feces, urine, and bile. • Main route is hepatic metabolism by excretion via bile and elimination through feces. [ABSTRACT FROM AUTHOR]

• Patients with cystic fibrosis are prone to electrolyte disturbances. • Guidelines state to monitor sodium status. • Sodium/creatinine ratio is an excellent surrogate marker for fractional sodium excretion. • Cut-offs for sodium/creatinine ratio are age related. Electrolyte disturbances are common in patients with cystic fibrosis (CF). Current guidelines on monitoring sodium status are based on research in a small group of infants and require blood sampling. The aim of this study was to evaluate urinary salt parameters as a surrogate for sodium-status in different age-groups. Blood and urine samples for electrolytes were collected from 222 patients followed at the Ghent University Hospital CF-center. Fractional sodium excretion (FENa) and several urinary parameters were calculated. Clinical characteristics did not differ according to sodium status, defined as FENa <0.5%. ROC analysis demonstrated that sodium/creatinine ratio (UNa/Creat) predicted the sodium status most accurately with high sensitivity and specificity (97 and 91% respectively). The UNa/Creat cut-off predicting a FENa <0.5% differed significantly according to age. The UNa/Creat is an excellent marker for the sodium status defined as a FENa <0.5%. However, different cut-offs according to age category should be applied. [ABSTRACT FROM AUTHOR]

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease. In this study, an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices. The plasma pharmacokinetics, tissue distribution, and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were systematically investigated. Despite its complicated structural composition, the absorption, distribution, metabolism, and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate. Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration, with very low oral bioavailability in rats (0.6%–1.6%) and dogs (4.5%–9.3%). Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues. Sodium oligomannate could penetrate the blood-cerebrospinal fluid (CSF) barrier of rats, showing a constant area under the concentration-time curve ratio (CSF/plasma) of approximately 5%. The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability, supporting that excretion was predominantly renal, whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats. Moreover, only 33.7% (male) and 26.3% (female) of the oral dose were recovered in the rat excreta within 96 h following a single oral administration, suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient. [Display omitted] • ADME profiles of sodium oligomannate oligosaccharides were indiscriminate. • An LC-MS/MS method was developed and validated for the ADME study of sodium oligomannate. • Sodium oligomannate was absorbed through paracellular transport with very low BA. • Approximately 5% of sodium oligomannate penetrated the blood–CSF barrier of rats. • The absorbed drug was excreted through the kidney; unabsorbed drug was excreted in feces. [ABSTRACT FROM AUTHOR]

Pharmacokinetics is the study of how the body handles an administered drug, including absorption, distribution, metabolism and excretion. Pharmacokinetic variation is when there is variability in the drug concentration at the effector site after administration of a standard dose. This can result in one dose of a drug being ineffective in one patient, but potentially toxic with unwanted side effects in another. There are four factors which are responsible for pharmacokinetic variation: absorption, distribution, metabolism and excretion. This article will review how physiological, pathological and pharmacological processes can influence all of these factors. [ABSTRACT FROM AUTHOR]

Background Assessing estimated sodium (Na) and potassium (K) intakes derived from 24-h urinary excretions compared with a spot urine sample, if comparable, could reduce participant burden in epidemiologic and clinical studies. Objectives In a 2-week controlled-feeding study, Na and K excretions from a 24-h urine collection were compared with a first-void spot urine sample, applying established algorithms and enhanced models to estimate 24-h excretion. Actual and estimated 24-h excretions were evaluated relative to mean daily Na and K intakes in the feeding study. Methods A total of 153 older postmenopausal women ages 75.4 ± 3.5 y participated in a 2-wk controlled-feeding study with a 4-d repeating menu cycle based on their usual intake (ClinicalTrials.gov Identifier: NCT00000611). Of the 150 participants who provided both a first-void spot urine sample and a 24-h urine collection on the penultimate study day, statistical methods included Pearson correlations for Na and K between intake, 24-h collections, and the 24-h estimated excretions using 4 established algorithms: enhanced biomarker models by regressing ln-transformed intakes on ln-transformed 24-h excretions or ln-transformed 24-h estimated excretions plus participant characteristics and sensitivity analyses for factors potentially influencing Na or K excretion (e.g. possible kidney disease estimated glomerular filtration rate <60 mL/min/1.73 m2). Results Pearson correlation coefficients between Na and K intakes and actual 24-h excretions were 0.57 and 0.38–0.44 for estimated 24-h excretions, depending on electrolyte and algorithm used. Enhanced biomarker model cross-validated R 2 (CVR2) for 24-h excretions were 38.5% (Na), 40.2% (K), and 42.0% (Na/K). After excluding participants with possible kidney disease, the CVR2 values were 43.2% (Na), 40.2% (K), and 38.1% (Na/K). Conclusions Twenty-four-hour urine excretion measurement performs better than estimated 24-h excretion from a spot urine as a biomarker for Na and K intake among a sample of primarily White postmenopausal women. [ABSTRACT FROM AUTHOR]

The PET hydrolase from Ideonella sakaiensis (Is PETase) is efficient for PET degradation, which provides a promising solution for environmental contamination by plastics. This study focuses on improving the excretion of Is PETase from E. coli by signal peptide (SP) engineering. A SP enhancer B1 (MERACVAV) was fused to the N-terminal of commonly-used SP (PelB, MalE, LamB, and OmpA) to mediate excretion of Is PETase. Strikingly, the modified SP B1OmpA, B1PelB, and B1MalE significantly increased the excretion of Is PETase, while Is PETase was basically expressed in periplasmic space without enhancer B1. The excretion efficiency of Is PETase mediated by B1PelB was improved by 62 folds compared to that of PelB. The hydrolysis of PET by crude Is PETase in culture solution was also enhanced. Furthermore, the amount of released MHET/TPA from PET by Is PETase was increased by 2.7 folds with pre-incubation of hydrophobin HFBII. Taken together, this work may provide a feasible strategy for the excretion and application of the Is PETase. [Display omitted] [ABSTRACT FROM AUTHOR]

Achieving complete nanoparticle (NP) clearance is a key consideration in the design of safe and translatable nanomedicines. Renal-clearable nano formulations must encompass the beneficial nanoscale functionalities whilst exhibiting clearance profiles like those of small-molecule therapeutics. Recent developments in the field have enabled the growth of novel renal-clearable NPs with transformable sizes that take advantage of alternative clearance mechanisms to achieve controlled and efficient renal excretion to improve potential clinical translation. [ABSTRACT FROM AUTHOR]

The field of nuclear imaging and therapy is rapidly progressing with the development of targeted radiopharmaceuticals that show rapid targeting and rapid clearance with minimal background. Unfortunately, they are often reabsorbed in the kidneys, leading to possible nephrotoxicity, limiting the therapeutic dose, and/or reducing imaging quality. The blocking of endocytic receptors has been extensively used as a strategy to reduce kidney radiation. Alternatively, the physicochemical properties of radiotracers can be modulated to either prevent their reuptake or promote the excretion of radiometabolites. Other interesting strategies focus on the insertion of a cleavable linker between the radiolabel and the targeting moiety or pretargeting approaches in which the targeting moiety and radiolabel are administered separately. In the context of this review, we will discuss the latest advances and insights on strategies used to reduce renal retention of low- to moderate-molecular-weight radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Monitoring and detecting individual cows' liveweight (LW) and liveweight change (LWC) are important for estimation of nutritional requirements and health management, and could be useful to measure short-term feed intake, water consumption, defecation, and urination. Walk-over weighing (WOW) systems can facilitate measurements of LW for these purposes, providing automated LW recorded at different times of the day. We conducted a field study to (1) quantify the contribution of feed and water intake, as well as urine and feces excretions, to short-term LWC and (2) determine the feasibility of stationary and WOW scales to detect subtle changes in LW as a result of feed and water intake, urination, and defecation. In this experiment, 10 cows walked through a WOW system and then stood individually on a stationary scale collecting weights at 10 and 3.3 Hz, respectively. Cows were offered 4 kg of feed and 10 kg of water on the stationary scale. For each animal, LW before and after eating and drinking was then calculated using different approaches. Liveweight change was calculated as the difference between the initial and final LW before and after eating and drinking for each statistical measure. The weights of feed intake, water consumption, urination, and defecation were measured and used as predictors of LWC. Urine and feces were collected from individual cows while the cow was on the scale, using a container, and weighed separately. The agreement between LWC measured using either stationary or WOW scales was assessed to determine the sensitivity of the scales to detect subtle changes in LW using the coefficient of determination (R2), Lin's concordance correlation coefficient (CCC), and mean bias. The prediction model showed that most of the regression coefficients were not significantly different from +1.0 for feed and water, or −1.0 for urine and feces. The R2 and CCC values demonstrated a satisfactory agreement between calculated and stationary LWC and values ranged from 0.60 to 0.92 and 0.71 to 0.94, respectively. A moderate agreement was achieved between calculated and automated LWC with R2 and Lin's CCC values of 0.45 to 0.63 and 0.60 to 0.74, respectively. Therefore, results demonstrated that new algorithms and data processing methods need to be continuously explored and improved to obtain accurate measurements of LW to measure changes in LW, especially from WOW scales. [ABSTRACT FROM AUTHOR]

Iron is essential for erythropoiesis and other biological processes, but is toxic in excess. Dietary absorption of iron is a highly regulated process and is a major determinant of body iron levels. Iron excretion, however, is considered a passive, unregulated process, and the underlying pathways are unknown. Here we investigated the role of metal transporters SLC39A14 and SLC30A10 in biliary iron excretion. While SLC39A14 imports manganese into the liver and other organs under physiological conditions, it imports iron under conditions of iron excess. SLC30A10 exports manganese from hepatocytes into the bile. We hypothesized that biliary excretion of excess iron would be impaired by SLC39A14 and SLC30A10 deficiency. We therefore analyzed biliary iron excretion in Slc39a14-and Slc30a10-deficient mice raised on iron-sufficient and -rich diets. Bile was collected surgically from the mice, then analyzed with nonheme iron assays, mass spectrometry, ELISAs, and an electrophoretic assay for iron-loaded ferritin. Our results support a model in which biliary excretion of excess iron requires iron import into hepatocytes by SLC39A14, followed by iron export into the bile predominantly as ferritin, with iron export occurring independently of SLC30A10. To our knowledge, this is the first report of a molecular determinant of mammalian iron excretion and can serve as basis for future investigations into mechanisms of iron excretion and relevance to iron homeostasis. [ABSTRACT FROM AUTHOR]

This study investigated whether the appropriate antibiotics therapy affects the fecal excretion time in pediatric salmonellosis of different severities and explored the factors associated with the fecal excretion time of nontyphoid Salmonella. Between 2012 and 2017, admitted children with nontyphoid salmonellosis who consented to receive consecutive stool cultures every 4–7 days until 2 consecutive negative results were obtained were enrolled. Patients were stratified into no, appropriate (bacteremia or severe patients receiving antibiotics active in vitro), and inappropriate antibiotics (patients with mild or moderate severity receiving antibiotics or severe receiving antibiotics resistant in vitro) therapy groups. A previously proposed severity score was used to classify the patients into severe, moderate, and mild severity classes. The demographics, clinical manifestations, laboratory data and severity were compared among the groups. To explore the factors associated with the fecal excretion time of nontyphoid Salmonella , univariate and multivariate analyses were performed using linear regression analysis. This study enrolled 126 children with nontyphoid salmonellosis; 58 and 18 in the mild and severe classes, respectively. The no, appropriate and inappropriate antibiotics therapy groups comprised 69, 24 and 33 patients, respectively. The mean fecal excretion time was 12.17 days. The appropriate antibiotics therapy group had comparable fecal excretion time with that of no antibiotics group. Age <1 year, increased white blood cell count, decreased hemoglobin, and inappropriate antibiotics therapy significantly prolonged fecal excretion time in univariate analysis (p < 0.05). The multivariate analysis showed that inappropriate antibiotics therapy and decreased hemoglobin significantly prolonged the fecal excretion time. Inappropriate antibiotics therapy and decreased hemoglobin prolong the fecal excretion time of nontyphoid Salmonella , whereas appropriate antibiotics therapy does not. Continuous monitoring of antibiotic resistance and judicious use of antibiotics in children with nontyphoid salmonellosis are necessary. [ABSTRACT FROM AUTHOR]

Measurement of urinary energy (UE) excretion is essential to determine metabolizable energy (ME) supply. Our objectives were to evaluate the accuracy of using urinary N (UN) or C (UC) to estimate UE and ultimately improve the accuracy of estimating ME. Individual animal data (n = 433) were used from 11 studies with Jersey cows at the University of Nebraska–Lincoln, where samples were analyzed after drying (n = 299) or on an as-is basis (n = 134). Dried samples resulted in greater estimated error variance compared with as-is samples, and thus only as-is samples were used for final models. The as-is data set included a range (min to max) in dry matter intake (11.6–24.6 kg/d), N intake (282–642 g/d), UE excretion (1,390–3,160 kcal/d), UN excretion (85–220 g/d or 20.6–59.5% of N intake), and UC excretion (130–273 g/d). As indicated by a bias in residuals between observed and predicted ME as dietary crude protein (CP; range of 14.9–19.1%) increased, the National Research Council dairy model did not accurately predict ME of diets, as dietary CP varied. The relationship between UE (kcal/d) and UN (g/d) excretion was linear and had an intercept of 880 ± 140 kcal. Because an intercept of 880 is biologically unlikely, the intercept was forced through 0, resulting in linear and quadratic relationships. The regressions of UE (kcal/d) on UN (g/d) excretion were UE = 14.6 ± 0.32 × UN, and UE = 20.9 ± 1.0 × UN − 0.0357 ± 0.0056 × UN2. In the quadratic regression, UE increased, but at a diminishing rate as UN excretion increased. As UC increased, UE linearly and quadratically increased. However, error variance was greater for regression with UC compared with UN as explanatory variables (8.42 vs. 7.42% of mean UE). The use of the quadratic regression between UN and UE excretion to predict ME resulted in a slope bias in ME predictions as dietary CP increased. The linear regression between UE and UN excretion removed slope bias between predicted ME and CP, and thus may be more appropriate for predicting UE across a wider range of dietary CP. Using equations to predict UE from UN should improve our ability to predict diet ME in Jersey cows compared with calculating ME directly from digestible energy. [ABSTRACT FROM AUTHOR]

• This study incorporated active renal excretion via OCT2 of model compound mepiquat in a physiologically based kinetic model. • The RPTEC cell line SA7K is proven to be a step forward in its use as a model to define kinetic parameters Vmax and Km for OCT2 uptake. • Translation of in vitro data to in vivo data is accompanied with usage of adequate scaling factors. The present study aimed at incorporating active renal excretion via the organic cation transporter 2 (OCT2) into a generic rat physiologically based kinetic (PBK) model using an in vitro human renal proximal tubular epithelial cell line (SA7K) and mepiquat chloride (MQ) as the model compound. The Vmax (10.5 pmol/min/mg protein) and Km (20.6 μM) of OCT2 transport of MQ were determined by concentration-dependent uptake in SA7K cells using doxepin as inhibitor. PBK model predictions incorporating these values in the PBK model were 6.7–8.4-fold different from the reported in vivo data on the blood concentration of MQ in rat. Applying an overall scaling factor that also corrects for potential differences in OCT2 activity in the SA7K cells and in vivo kidney cortex and species differences resulted in adequate predictions for in vivo kinetics of MQ in rat (2.3–3.2-fold). The results indicate that using SA7K cells to define PBK parameters for active renal OCT2 mediated excretion with adequate scaling enables incorporation of renal excretion via the OCT2 transporter in PBK modelling to predict in vivo kinetics of mepiquat in rat. This study demonstrates a proof-of-principle on how to include active renal excretion into generic PBK models. [ABSTRACT FROM AUTHOR]