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Aims: The formation of anti-drug antibodies (ADAs) during anti-tumor necrosis factor (anti-TNF) therapy is reported to lead to reducing serum drug levels, which may bring about a loss of response to treatment. Previous research has suggested an association between specific antibiotic classes and ADA formation during anti-TNF therapy. However, there are few studies specifically examining this association in Chinese inflammatory bowel disease (IBD) patients. Therefore, our study aimed to evaluate the possible effect of antibiotic use on ADA formation to anti-TNF therapy in Chinese patients with IBD. Methods: A total of 166 patients with IBD, including 149 with Crohn's disease (CD) and 17 with ulcerative colitis (UC), were included in this retrospective analysis. These patients were initially treated with anti-TNF therapy (infliximab or adalimumab) after January 2018 and reviewed with available ADA levels before October 2023. After univariable analysis of all the variables, a multivariate Cox proportional hazards model was used to assess the association between antibiotic use and ADA development. Results: Among 166 IBD patients treated with infliximab (108/166, 65.1%) or adalimumab (58/166, 34.9%), 31 patients (18.7%) were measured as positive ADA levels. Cox proportional hazard model demonstrated an increased risk of ADA formation in IBD patients who used ß-lactam-ß-lactamase inhibitor combinations (BL-BLIs) (HR = 5.143, 95%CI 1.136-23.270, p = 0.033), or nitroimidazoles (HR = 4.635, 95%CI 1.641-13.089, p = 0.004) during 12 months before the ADA test. On the contrary, a reduced risk was noted in patients treated with fluoroquinolones (HR = 0.258, 95% CI 0.072-0.924, p = 0.037). Moreover, the median serum infliximab or adalimumab concentration in patients with positive ADA levels was significantly lower than that in patients with negative ADA levels (infliximab: 0.30 vs. 1.85 µg/mL, p < 0.0001; adalimumab: 0.45 vs. 7.55 µg/mL, p = 0.0121). Conclusion: ADA development is associated with various antibiotic classes. BLBLIs and nitroimidazoles might increase the risk of ADA formation during anti-TNF therapy in Chinese IBD patients, while the treatment with fluoroquinolones could probably reduce such risk. There were certain limitations in the retrospective analysis of the study, therefore, the results are just for reference, and other studies are needed to further confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Serum drug concentration (SDC) is an important parameter used in drug efficacy and treatment follow-up. Aim: This study aimed to evaluate subtherapeutic, therapeutic and toxic SDCs, SDC measurement requests and demographic specialities (age and sex) for carbamazepine, phenytoin, phenobarbital, lithium and digoxin. Materials and Methods: This is a cross-sectional study, evaluating the outpatients' and inpatients' SDC data treated at Research and Application Hospital of Afyonkarahisar Health Sciences University between January 1, 2012 and February 28, 2019, and having SDC data. The relations between dependent and independent variables was evaluated with chi-square analysis and Students' T-test. P<0.05 was considered statistically significant. Results: A total of 3735 patients, 8946 admissions (mean: 41.1±26.6 years, 51.3% females) and 10158 SDCs were reviewed. Digoxin SDC was the most common measurement, at a rate of 33.7%. The highest number of SDC measurement was made in 2016 (n=1627). Subtherapeutic SDC rates were high for phenytoin, lithium, and digoxin (69.8%, 39.7%, 35.8%, respectively). Digoxin (16.2%) and phenobarbital (9.8%) were the drugs with the highest rate of toxic SDC. SDC increased for all drugs with increasing age, this was statistically significant for carbamazepine, lithium and digoxin (P<0.05). SDC for digoxin was found to be significantly higher in female sex (P<0.001). Conclusion: In this study, subtherapeutic and toxic SDC levels were examined. This study revealed the need for prospective studies evaluating Therapeutic Drug Monitoring (TDM) together with patient- and drug-related factors. [ABSTRACT FROM AUTHOR]

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Many viruses can cause infections in mink, including canine distemper virus, mink enteritis virus, and Aleutian disease virus. Current treatments are ineffective, and these infections are often fatal, causing severe economic losses. As antiviral drugs may effectively prevent and control these infections, recent research has increasingly focused on antiviral interferons. Herein, the gene encoding a mature mink interferon alpha (MiIFN-α) was synthesized according to the P. pastoris preference of codon usage and a recombinant plasmid, pPICZαA-MiIFN-α, was constructed. pPICZαA-MiIFN-α was linearized and transformed into the P. pastoris X33 strain, and zeocin-resistant transformants were selected. Protein expression was induced by methanol. SDS-PAGE and western blot analyses showed that a 25-kDa fusion protein was expressed in the culture supernatant. Antiviral activity of the expressed protein was determined using cytopathic effect inhibition (CPEI). The purified MiIFN-α significantly inhibited the cytopathic effect of vesicular stomatitis virus with a green fluorescent protein (VSV-GFP) in F81 feline kidney cells, with an antiviral activity of 6.4 × 107 IU/mL; it also significantly inhibited MEV replication in F81 cells. MiIFN-α antiviral activity against VSV-GFP was significantly reduced on treatment with pH 4 and pH 10 conditions for 24 h (p < 0.01). Serum MiIFN-α concentrations in rat were measured using enzyme-linked immune-sorbent assay; MiIFN-α concentrations in rat serum peaked at ~36 h after injection. A high dose of MiIFN-α was safe for use. There were no significant differences in body temperature, tissue changes, and lymphocyte, total white blood cell, and central granulocyte counts between the injected and control groups (p > 0.05). These findings lay a foundation for the large-scale production of recombinant MiIFNs.

BackgroundPosaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies.ObjectiveTo evaluate the cut-off serum concentration of PCZ for successful IFI prophylaxis in Chinese subjects.Patients and MethodsA total of 74 patients treated with induction chemotherapy (n = 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (n = 64), who received PCZ prophylactically as an oral suspension for >7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed.ResultsThe overall incidence of possible, probable, and proven IFIs was 13.5% (10/74), with five patients in the chemotherapy group and five in the HSCT group. The PCZ serum concentration in most patients (54/63) was in the range of 0.25–1.0 μg/ml, and this concentration range was significantly associated with the success rate of PCZ prophylaxis. A cut-off value of 0.47 μg/ml can be considered as an evaluation index for PCZ prophylaxis. Taking a proton pump inhibitor (PPI) would reduce the PCZ blood concentration, but not affect the IFD breakthrough point. PCZ treatment for hematopoietic malignancy or HSCT patients with a serum concentration of PCZ < 0.47 μg/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses.ConclusionThe serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of >0.47 μg/ml is highly recommended to avoid IFIs after chemotherapy or HSCT.Clinical Trial RegistrationChinese Clinical Trial Registry: ChiCTR1900026294.

Background: Posaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies. Objective: To evaluate the cut-off serum concentration of PCZ for successful IFI prophylaxis in Chinese subjects. Patients and Methods: A total of 74 patients treated with induction chemotherapy (n = 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (n = 64), who received PCZ prophylactically as an oral suspension for >7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed. Results: The overall incidence of possible, probable, and proven IFIs was 13.5% (10/74), with five patients in the chemotherapy group and five in the HSCT group. The PCZ serum concentration in most patients (54/63) was in the range of 0.25–1.0 μg/ml, and this concentration range was significantly associated with the success rate of PCZ prophylaxis. A cut-off value of 0.47 μg/ml can be considered as an evaluation index for PCZ prophylaxis. Taking a proton pump inhibitor (PPI) would reduce the PCZ blood concentration, but not affect the IFD breakthrough point. PCZ treatment for hematopoietic malignancy or HSCT patients with a serum concentration of PCZ < 0.47 μg/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses. Conclusion: The serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of >0.47 μg/ml is highly recommended to avoid IFIs after chemotherapy or HSCT. Clinical Trial Registration: Chinese Clinical Trial Registry: ChiCTR1900026294. [ABSTRACT FROM AUTHOR]

Interplay of pioneer transcription factor forkhead box A1 (FOXA1) and estrogen receptor has been implicated in sexual dimorphism in hepatocellular carcinoma (HCC), but etiological relevance of its polymorphism was unknown. In the case control study (1152 patients versus1242 controls), we observed significant increase in HCC susceptibility in hepatitis B virus carriers associated with a non-synonymous Thr83Ala variant of FOXA1 (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.11−1.48, for Ala83-containing genotype, after validation in an independent population with 933 patients versus 1030 controls), a tightly linked (CGC)5/6or7 repeat polymorphism at its promoter (OR 1.32; 95% CI 1.10–1.60, for (CGC)6or7-repeat-containing genotype), and their combined haplotype (OR 1.50; 95% CI 1.24–1.81, for (CGC)6or7−Ala83 haplotype). The susceptible FOXA1-Ala83 impairs its interaction with ERα, attenuates transactivation toward some of their dual target genes, such as type 1 iodothyronine deiodinase, UDP glucuronosyltransferase 2 family, polypeptide B17 and sodium/taurocholate cotransporting polypeptide, but correlates with strengthened cellular expression of α-fetoprotein (AFP) and elevated AFP serum concentration in HCC patients (n = 1096). The susceptible FOXA1 cis -variant with (CGC)6or7 repeat strengthens the binding to transcription factor early growth response 1 and enhances promoter activity and gene expression. Evolutionary population genetics analyses with public datasets reveal significant population differentiation and unique haplotype structure of the derived protective FOXA1-Thr83 and suggest that it may have undergone positive natural selection in Chinese population. These findings epidemiologically highlight the functional significance of FOXA1-ERα transcriptional program and regulatory network in liver cancer development. [ABSTRACT FROM AUTHOR]

Aims: The formation of anti-drug antibodies (ADAs) during anti-tumor necrosis factor (anti-TNF) therapy is reported to lead to reducing serum drug levels, which may bring about a loss of response to treatment. Previous research has suggested an association between specific antibiotic classes and ADA formation during anti-TNF therapy. However, there are few studies specifically examining this association in Chinese inflammatory bowel disease (IBD) patients. Therefore, our study aimed to evaluate the possible effect of antibiotic use on ADA formation to anti-TNF therapy in Chinese patients with IBD. Methods: A total of 166 patients with IBD, including 149 with Crohn's disease (CD) and 17 with ulcerative colitis (UC), were included in this retrospective analysis. These patients were initially treated with anti-TNF therapy (infliximab or adalimumab) after January 2018 and reviewed with available ADA levels before October 2023. After univariable analysis of all the variables, a multivariate Cox proportional hazards model was used to assess the association between antibiotic use and ADA development. Results: Among 166 IBD patients treated with infliximab (108/166, 65.1%) or adalimumab (58/166, 34.9%), 31 patients (18.7%) were measured as positive ADA levels. Cox proportional hazard model demonstrated an increased risk of ADA formation in IBD patients who used β-lactam-β-lactamase inhibitor combinations (BL-BLIs) (HR = 5.143, 95%CI 1.136-23.270, p = 0.033), or nitroimidazoles (HR = 4.635, 95%CI 1.641-13.089, p = 0.004) during 12 months before the ADA test. On the contrary, a reduced risk was noted in patients treated with fluoroquinolones (HR = 0.258, 95% CI 0.072-0.924, p = 0.037). Moreover, the median serum infliximab or adalimumab concentration in patients with positive ADA levels was significantly lower than that in patients with negative ADA levels (infliximab: 0.30 vs. 1.85 μg/mL, p < 0.0001; adalimumab: 0.45 vs. 7.55 μg/mL, p = 0.0121). Conclusion: ADA development is associated with various antibiotic classes. BL-BLIs and nitroimidazoles might increase the risk of ADA formation during anti-TNF therapy in Chinese IBD patients, while the treatment with fluoroquinolones could probably reduce such risk. There were certain limitations in the retrospective analysis of the study, therefore, the results are just for reference, and other studies are needed to further confirm our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Ju, Xu, Luo, Li and Wang.)

Background: The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated.Methods: Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection. Neurocognitive testing included measures of attention and executive function. fMRI was obtained during completion of two tasks, the continuous performance task (CPT) and the attention network task (ANT). Image analysis was performed using Statistical Parametric Mapping software, with contrasts targeting sustained attention, alerting, orienting, and conflict. All statistical tests were two-sided.Results: Compared with population norms, survivors demonstrated impairment on number-letter switching (P < .001, a measure of cognitive flexibility), which was associated with treatment intensity (P = .048). Task performance during fMRI was associated with neurocognitive dysfunction across multiple tasks. Regional brain activation was lower in survivors diagnosed at younger ages for the CPT (bilateral parietal and temporal lobes) and the ANT (left parietal and right hippocampus). With higher serum methotrexate exposure, CPT activation decreased in the right temporal and bilateral frontal and parietal lobes, but ANT alerting activation increased in the ventral frontal, insula, caudate, and anterior cingulate.Conclusions: Brain activation during attention and executive function tasks was associated with serum methotrexate exposure and age at diagnosis. These findings provide evidence for compromised and compensatory changes in regional brain function that may help clarify the neural substrates of cognitive deficits in acute lymphoblastic leukemia survivors. [ABSTRACT FROM AUTHOR]

Objectives: To report the efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults on concomitant anti-TB treatment and analyse factors associated with elevated concentrations in this specific population.Methods: Serum efavirenz concentrations in TB/HIV-coinfected Ugandan adults on efavirenz-based ART (600 mg daily) were measured onsite at 2, 8, 12 and 24 weeks of concomitant anti-TB treatment, including rifampicin. Genetic analysis was done retrospectively through real-time PCR by allelic discrimination (CYP2B6 516G>T, rs3745274). Univariable and multivariable logistic regression analyses were done to assess factors potentially associated with elevated efavirenz serum concentrations.Results: A total of 166 patients were included in the analysis. The median age was 34 (IQR = 30-40) years, 99 (59.6%) were male, the median CD4 cell count was 195 (IQR = 71-334) cells/mm3 and the median BMI was 19 (IQR = 17.6-21.5)  kg/m2. Almost half of all patients (82, 49.4%) had at least one efavirenz serum concentration above the reference range of 4 mg/L. The serum efavirenz concentrations of patients with genotype CYP2B6 516 TT were consistently above 4 mg/L and significantly higher than those of patients with GG/GT genotypes: CYP2B6 516 TT 9.6 mg/L (IQR = 7.3-13.3) versus CYP2B6 516 GT 3.4 mg/L (IQR = 2.1-5.1) and CYP2B6 516 GG 2.6 mg/L (IQR = 1.3-4.0) (Wilcoxon rank-sum test: P < 0.0001).Conclusions: A large proportion of our study participants had at least one efavirenz serum concentration >4 mg/L. The CYP2B6 516 TT genotype was the strongest predictor of high concentration. Physicians should be vigilant that efavirenz serum concentrations may be elevated in patients on concomitant anti-TB treatment and that individualized care is warranted whenever possible. [ABSTRACT FROM AUTHOR]

Background: Moxifloxacin is a second-line anti-TB drug that is useful in the treatment of drug-resistant TB. However, little is known about its target site pharmacokinetics. Lower drug concentrations at the infection site (i.e. in severe lung lesions including cavitary lesions) may lead to development and amplification of drug resistance. Improved knowledge regarding tissue penetration of anti-TB drugs will help guide drug development and optimize drug dosing.Methods: Patients with culture-confirmed drug-resistant pulmonary TB scheduled to undergo adjunctive surgical lung resection were enrolled in Tbilisi, Georgia. Five serum samples per patient were collected at different timepoints including at the time of surgical resection (approximately at Tmax). Microdialysis was performed in the ex vivo tissue immediately after resection. Non-compartmental analysis was performed and a tissue/serum concentration ratio was calculated.Results: Among the seven patients enrolled, the median moxifloxacin dose given was 7.7 mg/kg, the median age was 25.2 years, 57% were male and the median creatinine clearance was 95.4 mL/min. Most patients (71%) had suboptimal steady-state serum Cmax (total drug) concentrations. The median free moxifloxacin serum concentration at time of surgical resection was 1.23 μg/mL (range = 0.12-1.80) and the median free lung tissue concentration was 3.37 μg/mL (range = 0.81-5.76). The median free-tissue/free-serum concentration ratio was 3.20 (range = 0.66-28.08).Conclusions: Moxifloxacin showed excellent penetration into diseased lung tissue (including cavitary lesions) among patients with pulmonary TB. Moxifloxacin lung tissue concentrations were higher than those seen in serum. Our findings highlight the importance of moxifloxacin in the treatment of MDR-TB and potentially any patient with pulmonary TB and severe lung lesions. [ABSTRACT FROM AUTHOR]

Objective To summarize the clinical experience of patient diagnosed with Niemaoh-Pick disease being pregnant after liver transplantation. Methods Clinical data of one case of type B Niemaoh-Pick disease being pregnant after liver transplantation were retrospectively analyzed. Results The patient successfully underwent liver transplantation combined with splenic artery ligation on July 8, 2011. She was well recovered postoperatively. After surgery, she received conventional anti-rejection treatment, and gradually switched to use of tacrolimus at a dosage of 2.5 mg/d. The serum drug concentration was maintained at 2 ng/mL. In September 2015, she was successfully pregnant. On June 2, 2016, she delivered a male infant through cesarean section. She could breastfeed the infant in a low quantity early after delivery. Both the mother and infant were followed up until submission date. The mother was physically stable and the infant grew normally. Conclusions Patients diagnosed with Niemaoh-Pick disease can obtain favorable clinical outcomes of pregnancy and delivery after liver transplantation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effects of gender, age, dose and drug combination on steady-state plasma concentration in patients with olanzapine, so as to provide reference for clinical rational drug use. METHODS: Basic information such as gender, age, dose, drug combination and blood concentration in patients with olanzapine were collected from Brain Hospital Affiliated to Guangzhou Medical University from Feb. to Jul. 2018. Statistical analysis was performed on the data by using SPSS 16.0. RESULTS: Multiple linear regression showed that gender, age, and dose only explained 26.6% of the changes in olanzapine concentration. The serum drug concentration/dosage ration (C/D) of females were higher than that of males. There was no significant difference among different age groups. Drug combination of sodium valproate could significantly reduce the plasma concentration of olanzapine in patients, and the effects of clozapine on plasma concentration of olanzapine still need to be further studied. CONCLUSIONS: Olanzapine has a large difference in pharmacokinetics among individuals, and the influencing factors of blood concentration are complex. Patients are recommended to perform routine drug monitoring. The clinicians should adjust the drug dosage according to the blood concentration and clinical efficacy. [ABSTRACT FROM AUTHOR]

目的：比较万古霉素治疗新生儿感染在高血药浓度与低血药浓度状态下的肾毒性，评估高血药浓度下万古霉素的安全性。方法：研究对象为深圳市妇幼保健院2009年1月至2012年12月新生儿重症监护室（NICU）使用万古霉素治疗感染的新生儿。根据万古霉素血清谷浓度把新生儿分为A组（低谷浓度组，万古霉素谷浓度≤20 μg/ml）和B组（高谷浓度组，万古霉素谷浓度>20 μg/ml）。采用回顾性研究收集患儿的相关资料，包括临床诊断、并发症、血常规、生化检查、万古霉素使用剂量、给药方法、疗程、其他可能会影响肾功能的合并用药、血药浓度监测结果、临床结果等数据。结果：（1）在符合纳入标准的65例患儿中，万古霉素血清谷浓度≤20 μg/ml为47例（72.31％，A组），>20 μg/ml的有18例（27.69％，B组）。（2）65例万古霉素治疗的患儿中有13例（20.0%）发生了与万古霉素相关的肾毒性，其中A组5例（10.64%），B组8例（44.44%）。结论：高谷浓度比低谷浓度更容易发生肾毒性；新生儿个体差异很大，谷浓度与给药剂量并没有很好的线性关系。在NICU病房，临床医师大剂量超说明书使用万古霉素时一定要规范程序，严格管理，应该密切监测患儿的肾功能情况。 Objective:To compare the nephrotoxicity of low trough concentration and high trough concentration of vancomycin in the treatment of neonatal patients, and to evaluate the safety of high trough concentration of the drug. Methods: The research subjects were those neonatal patients treated with vancomycin in the neonate intensive care unit （NICU） of Shenzhen Maternity and Children Health Care Hospital from January 2009 to December 2012. In accordance with the serum trough concentrations of vancomycin, the neonates were divided into group A （the low trough concentration group, vancomycin≤20 μg/ml） and group B （the high trough concentration group, vancomycin＞20 μg/ml）. A retrospective survey was made and related medical data, such as clinical diagnosis, complications, blood routine, biochemical detection indices, dosage of vancomycin, routes of medication, courses of treatment, combined use of drugs that might affect nephrotoxicity, serum drug concentration detection results and clinical subsequences were collected for the study. Results: （1） Of the 65 neonatal patients that conformed to the included standards, 47 neonates （72.31%, group A） had a serum trough concentration of vancomycin≤20 μg/ml, and 18 neonates （27.69%, group B） had a serum trough concentration of vancomycin＞20 μg/ml. （2） Of the 65 neonatal patients treated with vancomycin, 13 neonates （20%） had vancomycin-associated nephrotoxicity. Of the 13 cases, 5 were in group A （10.64%） and 8 were in group B （44.44%）. Conclusion: Generally, neonates with higher trough concentrations of vancomycin were more likely to have nephrotoxicity, as compared to those with lower trough concentrations of the drug. Due to great differences in individuals, there was no good linearity between trough concentrations and medication dosages. Strict medical procedures should be followed and the renal function of neonatal patients should be closely monitored, when clinical physicians in the NICU gave large doses of vancomycin off label. [ABSTRACT FROM AUTHOR]

Objective:To explore the relationship between clinical efficacy and trough concentration of vancomycin in the treatment of neonatal bacterial sepsis （NBS）. Methods: Clinical medical data of 73 cases of NBS treated with vancomycin in the Department of Neonatology, Suzhou Hospital Affiliated to Nanjing Medical University were collected for the study. Clinical efficacy, bacterial elimination rate and trough concentration data were analyzed. Results: Total clinical effective rate and G+ bacterial elimination rate of vancomycin in the treatment of NBS were 86.30% and 91.78%,respectively. The average trough concentration of vancomycin was （12.57±6.83） mg/L after initial medication, and the rate of reaching the required standards was 41.10%. For the cases with the trough concentration at 10-20 mg/L, G+ bacterial elimination rate and clinical efficacy were significantly higher than those cases with the trough concentration lower than 10 mg/L （P=0.013, P=0.001）. The dosage of 24 cases was adjusted from our clinical experience about serum drug concentration. Further detection after dosage adjustment indicated that the trough concentration in only 13 cases （54.17%） was within the standard range. Conclusion: Clinical efficacy of vancomycin was highly associated with trough concentration of the drug. However, empirical medication could only achieve a low rate of high trough concentration standards. For this reason, dosage adjustment and patient-centered treatment were mandatory for better therapeutic effects. [ABSTRACT FROM AUTHOR]

We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLC-MS/MS) methods to quantify 25 antihypertensive drugs in serum samples. Patient-reported drug lists were collected, and drug concentrations were analysed in samples from 547 patients, half with uncontrolled hypertension, and all treated with ≥ 2 antihypertensive drugs. For sample preparation, serum was mixed with deuterated internal standards and acetonitrile and precipitated. Aliquots of the supernatant were injected on UHPLC-MSMS with a C18 reversed phase column. The mobile phase was 0.1 % HCOOH (formic acid) in water and 0.1 % HCOOH in acetonitrile (except in methanol for spironolactone/canrenone) at a flow rate of 0.4 mL/min. The calibrators and internal controls were prepared in Autonorm™. The calibration ranges were wide, and the models were linear or quadratic with squared correlation coefficients ≥ 0.97. The limits of detection and quantification, specificity, carry-over, and matrix effects were acceptable. The accuracy of the internal controls was in the range 85–121 %, and the intermediate precision for all drugs was 4–28 %. The patient-reported antihypertensive drug use and the detected serum drug concentrations were in accordance with that most frequently prescribed nationally. The percent non-detectable level was 5–10 % for bendroflumethiazide, doxazosin, nifedipine, and ramipril. Often the drug dose chosen was lower than the recommended maximum daily dose. We report the maximum (C max) and minimum (C min) drug concentrations after drug intake. The inter-individual pharmacokinetic variability at C min was 18-fold for hydrochlorothiazide, 22-fold for losartan carboxyl acid, 26-fold for amlodipine, 44-fold for candesartan, and 50-fold for valsartan. Our methods are suitable for measuring antihypertensive drugs in patient serum for therapy control. • Uncontrolled hypertension can be due to drug non-adherence and inadequate drug treatment. • We developed three UHPLC-MS/MS methods with simple serum sample preparation to quantify 25 frequently prescribed antihypertensive drugs. • We measured serum drug concentrations from 547 patients, half with uncontrolled hypertension and all treated with ≥ 2 antihypertensive drugs. • We described drug use, patients using the recommended maximum daily dose non-adherence, C max and C min ranges, and pharmacokinetic variability. • The methods are suitable for routine therapy control. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To establish RP-HPLC method for the determination of phenobarbital (PPB)， phenytoin (PHT) ， carbamazepine (CBZ) in serum. METHODS: The chromatographic column was Diamonsil Sum C18(250 mm X 4. 6 mm，5 μm)，the mobile phase was consisted of acetonitrile-water ( V : V = 33 : 67 ) ，With detective wavelength of 230 nm, flow rate of 1. 0 ml/min，column temperature of 30 °C and sample size of 20 &l. RESULTS； The calibration curves of three analytes were linear over the tested concentration range of 1. 0 μg/ml-80. 0 μg/ml (r > 0. 99) . The intra- and inter-day precision (RSD) was no more than 15% . The average recovery of PPB，PHT and CBZ were respectively 92. 2 % ，89. 1% and 89. 4% . CONCLUSIONS: The method was simple， sensitive and accurate. It was suitable for clinica1 monitoring of PPB，PHT and CBZ in serum. [ABSTRACT FROM AUTHOR]

Many viruses can cause infections in mink, including canine distemper virus, mink enteritis virus, and Aleutian disease virus. Current treatments are ineffective, and these infections are often fatal, causing severe economic losses. As antiviral drugs may effectively prevent and control these infections, recent research has increasingly focused on antiviral interferons. Herein, the gene encoding a mature mink interferon alpha (MiIFN-α) was synthesized according to the P. pastoris preference of codon usage and a recombinant plasmid, pPICZαA-MiIFN-α, was constructed. pPICZαA-MiIFN-α was linearized and transformed into the P. pastoris X33 strain, and zeocin-resistant transformants were selected. Protein expression was induced by methanol. SDS-PAGE and western blot analyses showed that a 25-kDa fusion protein was expressed in the culture supernatant. Antiviral activity of the expressed protein was determined using cytopathic effect inhibition (CPEI). The purified MiIFN-α significantly inhibited the cytopathic effect of vesicular stomatitis virus with a green fluorescent protein (VSV-GFP) in F81 feline kidney cells, with an antiviral activity of 6.4 × 10 7 IU/mL; it also significantly inhibited MEV replication in F81 cells. MiIFN-α antiviral activity against VSV-GFP was significantly reduced on treatment with pH 4 and pH 10 conditions for 24 h ( p < 0.01). Serum MiIFN-α concentrations in rat were measured using enzyme-linked immune-sorbent assay; MiIFN-α concentrations in rat serum peaked at ~36 h after injection. A high dose of MiIFN-α was safe for use. There were no significant differences in body temperature, tissue changes, and lymphocyte, total white blood cell, and central granulocyte counts between the injected and control groups ( p > 0.05). These findings lay a foundation for the large-scale production of recombinant MiIFNs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhang, Lu, Zou, Hu, Lian and Lu.)

Several epidemiological studies suggest that chronic alcoholics are at risk of viral infections. Clinical and basic research has demonstrated that alcohol not only worsens the natural history of chronic viral hepatitis, but also seems to interact with the viral replication cycle leading to an unusual serum virological profile and/or modification in the serum concentration of viral particles. Infections with hepatitis B and C viruses are a major risk for the development of hepatocellular carcinoma in excessive drinkers who should be protected against these viruses. [ABSTRACT FROM AUTHOR]

To investigate the means by which doxapram affects the control of ventilation, ventilatory function and P have been related to serum doxapram concentration during a 45-min infusion of doxapram hydrochloride in 7 healthy, conscious subjects under normoxic conditions. Serum doxapram concentrations increased during the infusion: 1.88, 2.48, 3.42, and 3.97 µg/ml after 5, 10, 30 and 45 min, respectively. The majority of significant changes in the measurements from the baseline were observed at 30 and 45 min: $${{\dot V}}_{{E}}$$ , V, P, P/end-tidal CO tension, V/T and blood pressure were increased, and end-tidal CO tension was decreased. No significant changes in Pdi, T/T, $${{\dot V}}_{{E}}$$ /P, and P/(V/T) were observed. A correlation was observed between the % increases in P and $${{\dot V}}_{{E}}$$ and doxapram concentration, and between $${{\dot V}}_{{E}}$$ and P. The doxapram-induced increase in $${{\dot V}}_{{E}}$$ appears to be caused by increased neural drive. It is related to the serum drug concentration in the conscious subject. [ABSTRACT FROM AUTHOR]

The central effects of single oral doses of phenobarbitone and phenytoin have been determined in six normal volunteers by measuring the critical flicker fusion threshold (CFF) under double-blind, placebo controlled conditions at intervals of up to 7 h after ingestion of the drug. Blood samples were taken at the same time for estimation of the serum concentration of the drugs by gas chromatography. Phenobarbitone in a dose of 180 mg produced a significant fall in CFF, and the time-course of this change mirrored the time-course of the serum concentration of the drug, which reached a peak of 21.8 µM (5.2 µg/ml) at 1.5 h. Phenytoin in doses of 200 mg, 300 mg and 400 mg produced no significant change in CFF even though an adequate serum concentration of the drug had been achieved (28.8 µM, 7.2 µg/ml, with the 400 mg dose). It was concluded that the two drugs differ in their action on the neural mechanisms tested by this procedure. [ABSTRACT FROM AUTHOR]

Background Vancomycin dosing guidelines recommend loading doses (LDs) (25–30 mg/kg TBW), and a maintenance regimen, usually started after a time period equal to the dosing interval. Studies of vancomycin exposure and nephrotoxicity conclude that a 0 to 24-hour area under the serum concentration–time curve (0–24AUC) > 677 mg-hour/L results in a 3- to 4-fold increased risk of nephrotoxicity (Zasowski EJ, Antimicrob Agents Chemother 2018). For vancomycin LDs we compare the calculated LD and the maintenance dose, and delay initiation of the maintenance regimen when the LD exceeds the daily maintenance dose by > 50%. This study assessed the pharmacokinetic outcomes from this technique. Methods We retrospectively reviewed 68 consecutive adult patients receiving therapeutic doses of vancomycin. Patient age, sex, height, weight, serum creatinine, and indication were used to calculate the daily dose/intervals for a steady-state 24-hr AUC of 400 or 600 mg-hour/L. The total 0–24AUC was calculated by adding the 0–24 AUC from a 25 mg/kg LD (max: 3 gm) to the 0–24AUC(s) for maintenance dose(s) within the first 24 hours. We compared the total 0-24AUC when the first maintenance dose was timed for the next dosing interval ("scheduled") to that when the maintenance dose was delayed according to our protocol ("delayed"). We tested the proportion of patients who would be exposed to a vancomycin 0-24AUC > 677 mg-hour/L. Results 16/68 patients were diagnosed with SSTI (goal 24 hr AUC: 400 mg-hour/L) and 52/68 with sepsis, bacteremia/endocarditis, or pneumonia (24 hr AUC: 600 mg-hour/L). Median daily maintenance dose was 1750 mg (range: 875–4,000 mg). For patients with a goal AUC of 400, the 0-24AUC was > 677 mg-hour/L in one patient using the "scheduled" process and in none of the patients using the "delayed" protocol. However, for patients with a goal AUC of 600, the 0-24AUC was > 677 mg-hour/L in 22/52 patients via the "scheduled" process vs. 4/52 patients via the "delayed" protocol. Conclusion For patients with severe gram-positive bacterial infections requiring aggressive dosing of vancomycin, delaying the start of maintenance dosing following a large LD is an effective way to ensure attainment of goal therapeutic AUC within the first 24 hr without placing the patient at increased risk for nephrotoxicity. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]