Search

The rapid advancement in ground and space based ionospheric measurements provide an opportunity to work on different earthquake precursors for lithosphere-ionosphere coupling hypothesis. In this paper, the peak plasma ionospheric frequency (foF2) for 90 days before/after the main shock of September 24, 2019 (M5.6) earthquake in Pakistan are studied for earthquake precursors from ionosonde stations located at Islamabad and Sonmiani. We implement the 30 days running median technique to detect the abnormality in foF2 over the epicenter of impending earthquake. A comprehensive analysis of these anomalies on two stations is performed in order to extract the maximum of these abnormalities in their respective regions. The deviation in hourly data in Sonmiani station shows significant variation within 10–20 days before the main shock, as most of the values within 5–10 days’ window are within the confidence limits. On the other hand, positive and negative deviations in the analysis of Islamabad station may be revealed as a possible signature of seismo-ionospheric anomalies. The major reason of these seismo-ionospheric anomalies is the distance between the ionosonde station and epicenter, where Islamabad station is close to the epicenter as compared to Sonmiani. It is noteworthy that both negative and positive deviations are observed before the M5.6 earthquake; however, the intensity of positive anomalies is more than negative anomalies. Moreover, severe positive deviation occurs within 10–20 days before the earthquake at the Sonmiani station. Also, there is no geomagnetic storm within 10 days before the earthquake which opposes the existence of seismo-ionospheric anomalies. The evidence supports that these seismo-ionospheric precursors are probably due to the lithospheric-ionospheric coupling.

Anaphylaxis is a medical emergency with adrenaline acknowledged as the first line therapy. It is therefore important that patients have access to self-injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators' websites and freedom of information requests. The data demonstrate that it takes at least 5-10 minutes to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time-to-peak concentration longer with increased skin-to-muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head-to-head comparisons, small numbers of study participants, and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes.

The aim of this study was to determine the pharmacokinetics and bioavailability of tolfenamic acid in goats after intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at 2 mg/kg dose. In this study, eight clinically healthy goats were used. The study comprised four periods, according to a crossover design with at least a 15-day washout period between treatments. Plasma concentrations of tolfenamic acid were determined by HPLC-UV, and the pharmacokinetic parameters were estimated using a non-compartmental method. Following IV administration, terminal elimination half-life, volume of distribution at steady state, and total clearance were 1.60 h, 0.37 L/kg, and 0.27 L/h/kg, respectively. The mean peak plasma concentration following IM, SC, and PO administrations was 1.77, 1.22, and 0.30 μg/ml, respectively. The mean bioavailability following IM, SC, and PO administrations was 64.46, 55.43, and 19.46%, respectively. The PO route, which exhibits both the low plasma concentration and bioavailability, is not recommended in goats. The IV, IM, and SC routes, which show comparable pharmacokinetic profiles, may be proposed for use in goats. However, the multi-dose and pharmacodynamic studies are necessary to establish more accurately its safety and efficacy in the goat.

The pharmacokinetics and bioavailability of furosemide were determined following intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations at 2.5 mg/kg dose in sheep. The study was conducted on six healthy sheep in a three-way, three-period, crossover pharmacokinetic design with a 15-day washout period. In first period, furosemide was randomly administered via IV to 2 sheep, IM to 2 sheep and SC to 2 sheep. In second and third periods, each sheep received furosemide via different routes of administration with the 15-day washout period. Plasma concentrations were determined using a high-performance liquid chromatography assay and analyzed by noncompartmental method. The mean total clearance and volume of distribution at steady state following IV administration were 0.24 L h-1 kg-1 and 0.17 L/kg, respectively. The elimination half-life was similar for all administration routes. The mean peak plasma concentrations of IM and SC administration were 10.33 and 3.18 μg/ml at 0.33 and 0.42 hr, respectively. The mean bioavailability of IM and SC administration was 97.91% and 37.98%, respectively. The IM injection of furosemide may be the alternative routes in addition to IV. However, further research is required to determine the effect of dose and route of administration on the clinical efficacy of furosemide in sheep.

We investigated the pharmacokinetic profile of co-administration of tulathromycin with rifampicin. Healthy male goats were allocated to three groups (n = 8) as Group A (single dose 2.5 mg/kg tulathromycin s.c.), B (10 mg kg-1 day-1 rifampicin p.o. daily for 7 days and single dose 2.5 mg/kg tulathromycin s.c. on 8th day), and C (10 mg kg-1 day-1 rifampicin p.o. daily for 21 days and single dose 2.5 mg/kg tulathromycin s.c. on 8th day). Blood samples were collected from jugular veins. Plasma samples were analyzed for tulathromycin by liquid chromatography-mass spectrometry (LC-MS/MS). Peak plasma concentration (Cmax ) values of tulathromycin were 1,390 ± 173, 958 ± 106, and 807 ± 116 ng/ml in groups A, B, and C, respectively. Cmax value of group A was greater than other groups (p

Purpose In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored. Methods Ten patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations. Results Peritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04). Conclusion In this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments. The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.

This study aimed to develop one novel meloxicam (MEL) oil suspension for sustained-release and compare the pharmacokinetic characteristics of it with MEL conventional formulation in pigs after a single intramuscular administration. Six healthy pigs were used for the study by a crossover design in two periods with a withdrawal interval of 14 days. Plasma concentrations of MEL were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetic parameters were calculated by noncompartmental methods. The difference was statistically significant (p < .05) between MEL oil suspension and MEL conventional formulation in pharmacokinetic parameters of mean residence time (6.16 ± 4.04) hr versus (2.66 ± 0.55) hr, peak plasma concentration (Cmax ) (0.82 ± 0.12) µg/ml versus (1.12 ± 0.22) µg/ml, time needed to reach Cmax (Tmax ) (2.33 ± 0.82) hr versus (0.59 ± 0.18) hr, and terminal elimination half-life (t1/2λz ) (3.74 ± 2.66) hr versus (1.55 ± 0.37) hr. The mean area under the concentration-time curve (AUC0-∝ ) of MEL oil suspension and MEL conventional formulation was 5.35 and 3.43 hr µg/ml, respectively, with a relative bioavailability of 155.98%. Results of the present study demonstrated that the MEL oil suspension could prolong the effective time of drugs in blood, thereby reducing the frequency of administration on a course of treatment. Therefore, the novel MEL oil suspension seems to be of great value in veterinary clinical application.

BACKGROUND Rapid control of agitation in medical settings is necessary for safety and provision of care. Inhaled loxapine achieves peak plasma levels within 2 minutes of administration and is FDA-approved for managing acute agitation. METHODS We examined the use of inhaled loxapine vs non-parenteral treatment as usual (TAU) in a psychiatric emergency service for consecutive patients with acute agitation or aggression. Data were collected retrospectively. T tests were used for continuous variables and Chi-square tests were used for categorical data. RESULTS A total of 61 patients received inhaled loxapine and 29 received TAU. Time to outcome for patients receiving inhaled loxapine was 21 ± 21 minutes compared with 121 ± 206 minutes for TAU (t =-2.61; P = .014). At outcome, 89% of patients treated with loxapine experienced symptom resolution, compared with 69% of TAU (Chi-square = 17.4, P < .0001). Ten percent of patients receiving loxapine had no change in symptoms and 1% had worsening symptoms vs 14% in the TAU group who experienced no change in symptoms (z = 0.5, not significant), and 17% who described worsening symptoms (z = 6153.9, P < .0001). CONCLUSIONS The rapid absorption of inhaled loxapine is associated with a 6-fold faster and more robust symptom control.

We report a case of a 41-year-old male with anticipated difficult airway undergoing a repair of a bilateral radial fracture under bilateral sequential brachial plexus block. Anesthesiologists are reluctant to perform bilateral blocks because of the fear of complications like diaphragmatic paralysis, local anesthetic (LA) toxicity, and pneumothorax. We advise that with the correct application of LA pharmacokinetics, careful patient selection and usage of ultrasound, bilateral blocks can be done safely. We used chloroprocaine as an LA in one of the blocks to reduce the dose required for the more toxic LAs. chloroprocaine’s fast metabolism also helped us to prevent the overlapping of peak plasma concentration of different LAs. To our knowledge, this is the first reported case in the literature where chloroprocaine was used for bilateral brachial plexus block.

We prospectively evaluated the Bard PowerFlow Implantable Apheresis IV Port in four patients undergoing outpatient therapeutic plasma exchange over 18 to 97 days. Three had bilateral internal jugular access ports, and one had a single left internal jugular access port for the inlet line with return via antecubital vein. Two patients receiving 5% albumin as replacement fluid achieved peak inlet flow of 99 ± 5 mL/min and 101 ± 6 mL/min, and peak plasma flow of 53 ± 6 and 47 ± 6 mL/min, respectively. Two patients receiving plasma as replacement fluid achieved peak inlet flow of 46 ± 7 and 85 ± 4 mL/min and peak plasma flow of 27 ± 3 and 35 ± 4 mL/min, respectively. Apheresis nurses accessed the ports on the first attempt in all procedures. Pressure alarms occurred in 6 of 47 procedures and were easily resolved by lowering the inlet rate by 10% in 5 of them. The PowerFlow shows promise as an implantable venous access device for apheresis.

PICO question In reducing surgical recovery time in rabbits (Oryctolagus cuniculus), should doses exceeding 0.2 mg/kg of oral meloxicam be given and is twice daily administration more effective than a single daily dose? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed Nine papers were critically reviewed, yet no studies were found to directly investigate the effects of twice daily dosing with meloxicam postoperatively in rabbits. There were five descriptive, non-comparative case series; two nonblinded parallel group randomised control trials; one blinded, placebo-controlled parallel group randomised trial and one prospective, randomised crossover trial Strength of evidence Weak Outcomes reported The current recommended oral dose of meloxicam in rabbits of 0.2–0.3 mg/kg once a day was consistently described as inadequate for postoperative analgesia following surgery (Delk et al., 2014). Instead, higher doses of 1–1.5 mg/kg were required to reach a similar peak plasma concentration as found to be clinically effective in other species, such as canines, and provide a better degree of analgesia in rabbits (Montoya et al., 2004; and Delk et al., 2014). Although no studies were found evaluating twice daily administration of meloxicam, the available evidence suggests a dose exceeding 0.2–0.3 mg/kg daily is required for adequate postoperative analgesia in rabbits. Whether this increased dose could be given twice daily should be investigated, providing scope for future research Conclusion Further studies are required to directly assess the benefits of twice daily oral meloxicam. However, it is possible that a dose exceeding 0.2–0.3 mg/kg is required and therefore higher doses should be considered in these studies How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Despite having adequate solubility properties, bioequivalence (BE) studies performed on immediate release formulations containing BCS1/3 drugs occasionally fail. By systematically evaluating a set of 17 soluble drugs where unexpected BE failures have been reported and comparing to a set of 29 drugs where no such reports have been documented, a broad assessment of the risk factors leading to BE failure was performed. BE failures for BCS1/3 drugs were predominantly related to changes in Cmax rather than AUC. Cmax changes were typically modest, with minimal clinical significance for most drugs. Overall, drugs with a sharp plasma peak were identified as a key factor in BE failure risk. A new pharmacokinetic term (t½Cmax) is proposed to identify drugs at higher risk due to their peak plasma profile shape. In addition, the analysis revealed that weak acids, and drugs with particularly high gastric solubility are potentially more vulnerable to BE failure, particularly when these features are combined with a sharp Cmax peak. BCS3 drugs, which are often characterised as being more vulnerable to BE failure due to their potential for permeation and transit to be altered, particularly by excipient change, were not in general at greater risk of BE failures. These findings will help to inform how biowaivers may be optimally applied in the future.

The aim of this study was to determine the pharmacokinetics of letrozole and its effect on FSH and LH concentrations after single (IV, IM, SC) and repeated IV doses in anestrous ewes. This study was conducted in experiments 1 and 2 by randomly dividing 24 healthy Akkaraman ewes in anestrus into two equal groups. In experiment 1, the pharmacokinetics of letrozole following single IV, IM, and SC administration at 1 mg/kg dose and its effect of a single IV dose on plasma FSH and LH concentration were determined. In experiment 2, the effect of repeated IV doses of letrozole on FSH and LH concentrations was established. Plasma concentration of letrozole was measured using high-performance liquid chromatography, and pharmacokinetic parameters were calculated by non-compartmental analysis. FSH and LH concentrations were quantified using ELISA. The elimination half-life (t1/2ʎz) for IV, IM, and SC routes were 9.94, 37.29, and 41.07 h, respectively. The IV route for letrozole had a total clearance of 0.11 L/h/kg and a volume of distribution at a steady state of 1.50 L/kg. The peak plasma concentration was 0.11 μg/mL for the IM route and 0.14 μg/mL for the SC routes. The bioavailability was 55.18% for the IM route and 75.34% for the SC route. Letrozole following single and repeated (every 24 h for 3 days) IV administrations at 1 mg/kg dose did not affect LH concentration in anestrous ewes but caused an increase in the FSH concentration. This increase in FSH concentration may create a potential for the use of letrozole in ovarian superstimulation protocols. Favorable pharmacokinetic properties (long t1/2ʎz and good bioavailability) of letrozole for IM and SC routes require further investigation before use in estrus induction or estrus synchronization protocols in sheep.

The pharmacokinetics and bioavailability of tolfenamic acid were determined in geese (Anser cygnoides) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral administrations at 2 mg/kg dose. In this study, eight healthy geese (3.5 ± 0.5 kg) were used. The study was performed in four periods according to a crossover design with a 15-day washout period between two administrations. The plasma concentrations of tolfenamic acid were analyzed using HPLC-UV, and pharmacokinetic parameters were calculated by noncompartmental analysis. The elimination half-life was 1.73, 2.51, 2.34, and 2.31 hr for IV, IM, SC, and oral routes, respectively. The volume of distribution at steady state and total clearance after IV administration were 0.25 L/kg and 0.16 L hr-1 kg-1 , respectively. The peak plasma concentrations of tolfenamic acid after IM, SC, and oral administrations were 4.89, 2.94, and 2.92 μg/ml at 0.25, 0.75, and 1 hr, respectively. The bioavailability was 87.91, 77.87, and 76.03% for the IM, SC, and oral routes, respectively. Tolfenamic acid, which exhibits the good bioavailability and plasma concentration following IM, SC, and oral administrations at 2 mg/kg dose, may be useful in the treatment of inflammatory disease conditions in geese.

A single-dose disposition kinetics for tildipirosin was evaluated in clinically healthy ewes (n = 6) after intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration of a commercial formulation. Tildipirosin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Plasma concentration-time data was calculated by non-compartmental pharmacokinetic methods. The apparent volume of distribution (Vz) of tildipirosin after IV administration was 5.36 &plusmn, 0.57 L/kg suggesting a wide distribution in tissues and inside the cells. The elimination half-life (t&frac12, &lambda, z) was 17.16 &plusmn, 2.25, 23.90 &plusmn, 6.99 and 43.19 &plusmn, 5.17 h after IV, IM and SC administration, respectively. Following IM administration, tildipirosin was rapidly absorbed (tmax = 0.62 &plusmn, 0.10 h) even to a greater extent than after SC administration. Time to reach peak concentration (tmax) and peak plasma concentrations (Cmax) differed significantly, but both parameters showed a more significant variability after SC than after IM administration. Bioavailabilities after extravascular administration were high (&gt, 70%). Therefore, given general adverse reactions that were not observed in any ewe and favourable pharmacokinetics, tildipirosin could be effective in treating bacterial infections in sheep.

Canagliflozin (CNZ) is the first sodium-glucose co-transporter-2 inhibitor approved for treatment of type 2 diabetes mellitus. In the proposed work, a sensitive, rapid and validated high-performance thin-layer chromatography (HPTLC) method was established for the estimation of CNZ in human plasma for the first time. HPTLC analysis of CNZ and internal standard (sildenafil) was performed on glass coated silica gel 60 F254 HPTLC plates using a binary mixture of chloroform-methanol 9:1 (%, v/v) as the mobile phase. Densitometric detection was done at 295 nm. Retardation factor values were obtained as 0.22 and 0.52 for the CNZ and the IS, respectively. The linearity range of CNZ was obtained as 200-3,200 ng/ml. A simple protein precipitation method was used for the extraction of analyte from plasma using methanol. The proposed HPTLC technique was validated for linearity, accuracy, precision and robustness. The proposed HPTLC technique was successfully utilized for the assessment of pharmacokinetic profile of CNZ in rats after oral administration. After oral administration, the peak plasma concentration of CNZ was obtained as 1458.01 ng/ml in 2 h. The proposed HPTLC method could be applied to the study of the pharmacokinetic profile of pharmaceutical formulations containing CNZ.

To evaluate the potential for ethnicity‐related differences in ataluren pharmacokinetics (PK) and safety, a phase 1 single‐dose study was conducted in 48 healthy (24 Japanese and 24 Caucasian subjects), nonsmoking male volunteers who were equally divided into 3 cohorts of oral doses at 5, 10, and 20 mg/kg. Blood samples were collected until 48 hours postdose. PK results demonstrated rapid absorption of ataluren, with peak plasma levels (Cmax) being attained between 0.875 and 2.5 hours after dosing. The mean Cmax and area under the concentration‐time curve (AUC(0‐last)) increased with each increasing dose level in both Japanese and Caucasian subjects. Although the Cmax was similar across all subjects at each dose regardless of ethnicity, Japanese subjects had a mean AUC(0‐last) approximately 14% to 34% lower than that of Caucasian subjects across the 3 dose levels. This difference was likely due to the higher variability of AUC values in Caucasian subjects and the relatively small study population. In conclusion, similar ataluren PK profiles were observed in healthy Japanese and Caucasian subjects following single oral administration of ataluren at all dose levels.

Background Although the demand for esomeprazole is increasing in veterinary medicine, the pharmacokinetics (PK) and pharmacodynamics of esomeprazole have been described in only a few studies. Objective To determine the PK of 0.5 and 1 mg/kg esomeprazole administered IV q12h and to investigate its effects on intragastric pH in healthy dogs. Animals Six adult Beagles. Methods Open-label, randomized, and crossover design. The dogs received 0.5 or 1 mg/kg esomeprazole IV q12h for 48 hours. Plasma concentrations of esomeprazole were measured by high-performance liquid chromatography-tandem mass spectrometry. Intragastric pH was determined using the Bravo pH monitoring system and recorded as mean percentage time (MPT) for which pH was ≥3 and ≥4 for 24 hours in each group. Results The peak plasma concentration and area under the curve from the time of dosing to the last measurable concentration in the 1 mg/kg group were higher than those in the 0.5 mg/kg group. However, when the dosage normalized, intergroup differences were not significant. The MPTs for which intragastric pH was ≥3 and ≥4 for 48 hours were 88% ± 7% and 81% ± 9% for the 0.5 mg/kg group and 90% ± 9% and 85% ± 11% for the 1 mg/kg group, respectively, with no significant intergroup differences. Conclusions and clinical importance The pharmacokinetic parameters and acid suppressant effect for 0.5 and 1 mg/kg esomeprazole were not significantly different. Furthermore, the efficacy of esomeprazole 0.5 mg/kg IV q12h was sufficient to increase intragastric pH in Beagles.

Ethanamizuril (EZL) is a novel triazine anticoccidial compound that has high anticoccidial activity in chickens. In order to treat coccidiosis rationally in poultry, a detection method was developed for ethanamizuril in broiler plasma, and then the pharmacokinetics studies were performed in broilers after oral administration of different dose levels. Ethanamizuril was administered as single oral doses at low (0.67 mg kg−1 BW), medium (1.33 mg kg−1 BW) and high (6.67 mg kg−1 BW) levels in which the medium dose was that recommended in clinics. Plasma concentrations of ethanamizuril were determined using ultra-high performance liquid chromatography and the data were analyzed with a non-compartmental model. Peak plasma concentrations of ethanamizuril were (2.16±0.57), (3.91±0.71), and (23.71±5.02) mg L−1 at (5.17±1.80), (4.60±2.12), and (4.60±2.12) h, respectively. The terminal elimination half-lives (t1/2λz) for ethanamizuril were (10.84±2.59), (10.66±2.47), and (13.34±3.10) h after oral administration at low, medium and high doses, respectively. The areas under the concentration-time curve (AUC0–t) were (37.68±6.87), (73.19±9.18), and (485.76±125.10) mg L−1 h with mean residence times (MRT0–t) of (14.79±3.03), (15.57±3.69), and (20.22±4.01) h at the 3 dosages, respectively. Ethanamizuril was absorbed rapidly and eliminated slowly. A comparison across the dose range indicated that the time to reach peak plasma concentration (Tmax) values were similar while peak plasma concentration (Cmax) and AUC0–t were positively correlated with increasing dosages. This study of the pharmacokinetics of an ethanamizuril solution in chickens provides a theoretical basis for the rational use in the clinic.

PUFA modulate hypothalamic–pituitary–adrenal (HPA) axis activity and cortisol concentrations and therefore affect physiological stress responses and the regulation of energy balance in the short- and long-term. Especially dietary intake ofn-3 PUFA and a loweredn-6:n-3 ratio are highly encouraged due to beneficial and diminishing effects on basal cortisol secretions. However, the time of such effects to occur and how plasma PUFA patterns affect cortisol concentrations in the short-term was rarely investigated. In order to address this, we supplemented forty male and forty female guinea pigs with diets high in the essential PUFAα-linolenic acid (ALA, 18 : 3n-3) and linoleic acid (LA, 18 : 2n-6) for 20 d. Saliva cortisol concentrations in relation to altering plasma PUFA patterns during this time span were analysed in a repeated measurement design both during basal conditions (individual housing) in 5-d intervals and during stressful social confrontations. We detected very fast plasma PUFA accumulation rates, corresponding to the major dietary PUFA, which resulted in plasma PUFA plateau phases after 10 d. ALA negatively and LA positively affected saliva cortisol concentrations throughout the study. A positive effect of the plasman-6:n-3 ratio on saliva cortisol concentrations was detected during peak plasma PUFA accumulations and social confrontations, while no effects were detected in relation to plasma PUFA plateau phases. These results suggest that the plasman-6:n-3 ratio diminishes HPA axis activity during altered physiological conditions only and highlights the importance of altering plasma PUFA patterns for HPA axis functions and the control of energy balance and physiological stress.

Ethanamizuril is a new triazine compound that displays potent anticoccidial activity against chicken coccidiosis caused by Eimeria tenella. We studied the pharmacokinetics of ethanamizuril in rats and chickens after single oral doses of one, two and three times the minimum effective dose Ethanamizuril was readily absorbed at all three doses and the plasma concentration reached was maximal within 5h and progressively declined over time. The mean peak plasma concentrations (Cmax) and the area under the concentration-time curve (AUC) were both dose-dependent. These results provide pharmacokinetic profiles of ethanamizuril for future preclinical studies and clinical use.

Simultaneous changes in several physiological factors may contribute to the large pharmacokinetic (PK) variability of vancomycin. This study was designed to systematically characterize the effects of multiple physiological factors to the altered PK of vancomycin observed in special populations. A vancomycin physiologically based pharmacokinetic (PBPK) model was developed as a PK simulation platform to quantitatively assess the effects of changes in physiologies to the PK profiles. The developed model predicted the concentration-time profiles in healthy adults and diseased patients. The implementation of developmental changes in both renal and non-renal elimination pathways to the pediatric model improved the predictability of vancomycin clearance. Simulated PK profiles with a 50% decrease in cardiac output (peak plasma concentration (Cmax ), 59.9 ng/mL) were similar to those observed in patients before bypass surgery (Cmax , 55.1 ng/mL). The PBPK modeling of vancomycin demonstrated its potential to provide mechanistic insights into the altered disposition observed in patients who have changes in multiple physiological factors.

The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60–70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036–0.12; 95% CI] or 21.9 ng/ml [12.1–40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection., Graphical abstract Image 1, Highlights • A novel high-throughput screen for Sarcocystis neurona growth is developed. • Eighteen novel inhibitory compounds are identified from a drug repurposing library. • Dantrolene, a currently available equine drug, also inhibits parasite growth. • Identified inhibitory compounds share activity against related parasites.

Amino acids from meals peak in the plasma at ~180 minutes postprandial. Conversely, amino acids from rapidly digestible whey protein appear in the plasma within 15 minutes and peak at 60 minutes postprandial. Therefore, we hypothesized that consuming a 20-g whey protein snack 2 hours after a standard mixed-macronutrient, lower protein breakfast (10 g) would result in peak and composite postprandial plasma essential amino acid (EAA) responses that were not different from consuming a 30-g protein breakfast alone. Using a randomized, crossover design, 12 subjects (6 men, 6 women; age: 29 ± 1 y; BMI: 26.0 ± 1.0 kg/m2; mean ± SE) completed three 330-minute trials in which they consumed breakfasts containing (i) 10 g of protein (10-PRO, control), (ii) 30 g of protein (30-PRO), and (iii) 10 g of protein followed by 20 g of whey protein isolate 120 minutes later (10/20-PRO). For both 30-PRO and 10/20-PRO, EAA peaked 180 minutes after breakfast, with greater peak concentrations for 10/20-PRO than 30-PRO (Tukey adjusted, P < .0001). Essential amino acid positive incremental areas under the curve (iAUCpos) over 300 minutes were not different between 30-PRO and 10/20-PRO. Consuming a rapidly digested whey protein snack 2 hours after a slowly digested, lower protein breakfast resulted in a greater peak plasma EAA concentration but comparable plasma EAA availability than consuming a single higher protein breakfast.

Aim: To further characterize the pharmacokinetics of Xtampza® ER. Subjects & methods: This was an open-label, randomized, active-controlled, five-treatment, five-period, naltrexone-blocked, cross-over study. Healthy subjects received five equivalent oxycodone doses: Xtampza ER (intact or crushed), OxyContin® (intact or crushed) or immediate-release (IR) oxycodone (crushed). Blood samples were collected to assess oxycodone concentrations. Results: Crushed and intact Xtampza ER resulted in lower peak plasma concentrations compared with crushed oxycodone IR; crushed and intact Xtampza ER were bioequivalent. Crushed OxyContin exhibited a rapid increase in plasma oxycodone and was bioequivalent to crushed oxycodone IR. Conclusion: This second pharmacokinetic study demonstrated that Xtampza ER maintains its ER properties after crushing, unlike OxyContin, which failed to retain its ER properties after crushing. ANZCTR registration number: ACTRN12614000613606

Quinocetone (QCT), an antimicrobial growth promoter, is widely used in food-producing animals. However, information about pharmacokinetics (PK) of QCT in ducks still remains unavailable up to now. In this study, QCT and its major metabolites (1-desoxyquinocetone, di-desoxyquinocetone and 3-methyl-quinoxaline-2-carboxylic) in ducks were studied using a simple and sensitive UHPLC-MS/MS assay. Twenty ducks were divided into two groups. (n = 10/group). One group received QCT by oral administration at dose of 40 mg/kg while another group received QCT intravenously at 10 mg/kg. Plasma samples were collected at various time points from 0 to 96 hr. QCT and its major metabolites in duck plasma samples were extracted by 1 ml acetonitrile and detected by UHPLC-MS/MS, with the gradient mobile phase that consisted of 0.1% formic acid in water (A) and acetonitrile (B). A noncompartment analysis was used to calculate the PK parameters. The results showed that following oral dosing, the peak plasma concentration (Cmax ) of QCT was 32.14 ng/ml and the area under the curve (AUCINF_obs) was 233.63 (h ng)/ ml. Following intravenous dosing, the Cmax , AUCINF_obs and Vss_obs were 96.70 ng/ml, 152.34 (h ng)/ ml and 807.00 L/kg, respectively. These data indicated that the QCT was less absorbed in vivo following oral administration, with low bioavailability (38.43%). QCT and its major metabolites such as 1-desoxyquinocetone and 3-methyl-quinoxaline-2-carboxylic were detected at individual time points in individual ducks, while the di-desoxyquinocetone was not detected in all time points in all ducks. This study enriches basic scientific data about pharmacokinetics of QCT in ducks after oral and intravenous administration and will be beneficial for clinical application in ducks.

The pharmacokinetic parameters of levamisole were determined in the Caspian salmon after intramuscular (IM), oral by gavage, and oral by feed administrations. Eighty-one healthy fish in three different groups received levamisole at the dose of 25 mg/fish by each route. Blood samples were collected at time points of 0, 0.5, 1, 2, 4, 6, 12, 14, and 24 hr after administrations. Plasma levamisole concentrations were measured by a validated high-performance liquid chromatography (HPLC) assay and were analyzed using a noncompartmental approach. The mean terminal half-life was 4.56, 3.95, and 2.91 hr for IM, gavage and feed routes, respectively. The peak plasma concentration for IM, gavage, and feed routes of levamisole were 35.53, 4.63, and 8.36 µg/ml, respectively, at the time of 0.25 for IM, and 1 hr for gavage and feed. The relative bioavailability for gavage and feed routes was 54.80 and 69.30. The similar bioavailability for gavage and feed might be indicative of similar efficacy for these routes of administrations. Further studies are warranted to evaluate the absolute oral bioavailability and the effective dose in Caspian salmon.

Levofloxacin pharmacokinetic profiles were evaluated in 6 healthy female rabbits after intravenous (I/V), intramuscular (I/M), or subcutaneous (S/C) administration routes at a single dose of 5 mg/kg in a 3 × 3 cross-over study. Plasma levofloxacin concentrations were detected using a validated Ultra Performance Liquid Chromatography method with a fluorescence detector. Levofloxacin was quantifiable up to 10 h post-drug administration. Mean AUC0-last values of 9.03 ± 2.66, 9.07 ± 1.80, and 9.28 ± 1.56 mg/h*L were obtained via I/V, I/M, and S/C, respectively. Plasma clearance was 0.6 mL/g*h after I/V administration. Peak plasma concentrations using the I/M and S/C routes were 3.33 ± 0.39 and 2.91 ± 0.56 μg/mL. Bioavailability values, after extravascular administration were complete, - 105% ± 27% (I/M) and 118% ± 40% (S/C). Average extraction ratio of levofloxacin after I/V administration was 7%. Additionally, levofloxacin administration effects on tear production and osmolarity were evaluated. Tear osmolarity decreased within 48 h post-drug administration. All 3 levofloxacin administration routes produced similar pharmacokinetic profiles. The studied dose is unlikely to be effective in rabbits; however, it was calculated that a daily dose of 29 mg/kg appears effective for I/V administration for pathogens with MIC < 0.5 μg/mL.

Objective To compare the cosmetic result of the PEAK Plasma Blade with traditional scalpel in patients who had primary cesarean delivery by using POSAS (Patient and Observer Assessment Scale). Material and methods Fourty women between 20 and 40 years, who were planning to have primary cesarean delivery, were randomized for skin incision with PEAK Plasma Blade (n:20) and with scalpel (n:20) were blinded to their group allocation. At six months, the cosmetic outcome of the cesarean scar was assessed using the POSAS. Subjective scar rating was performed using the patient component of the POSAS. Objective scar assessment was performed by an observer dermatologist blinded to the patient's group allocation. Results The observer scores (p = 0,003), patient scores (p = 0,001) and the total scores (p = 0,001) of the POSAS scale were significantly lower in favor of the Peak Plasma Blade group with respect to the scalpel group. Conclusion The PEAK Plasma Blade has superior cosmetic outcome compared to traditional scalpel skin incision at cesarean section.

Background The purpose was to investigate the effect of caffeine (CAF) mouth rinse on peak power (PP), mean power (MP), peak power relative to body mass (rel PP), mean power relative to body mass (rel MP), fatigue index (FI) and anaerobic contribution in the Wingate Test. Methods Ten healthy men (age: 24.8±3.7 years; body mass: 71.0±7.8 kg; height: 170±3 cm; body fat: 17.02±4.9%; VO2max: 44.15±5.5 ml·kg-1·min=) were recruited. A randomized, double-blind, cross-over design was employed. Participants were instructed to complete Wingate Test in the fastest time possible under 2 conditions: CAF (25 ml of mint syrup with 1.2% of CAF, equivalent to 300 mg of CAF) and placebo (PLA) (25 ml of mint syrup without CAF). Results There was no difference at PP (P=0.66), MP (P=0.16), rel PP (P=0.82), rel MP (P=0.18), FI (P=0.19), anaerobic alactic (P=0.71), anaerobic lactic (P=0.25), total energy expenditure (P=0.41) and peak plasma lactate concentration (P=0.57). Conclusions CAF mouth rinse did not increase peak power (PP), mean power (MP), peak power relative to body mass (rel PP), mean power relative to body mass (rel MP), Fatigue Index (FI) nor anaerobic contribution in the Wingate Test.

In quantitative systems pharmacology (QSP) and physiologically‐based pharmacokinetic (PBPK) modeling, data digitizing is a valuable tool to extract numerical information from published data presented as graphs. To quantify their relevance, a literature search revealed a remarkable mean increase of 16% per year in publications citing digitizing software together with QSP or PBPK. Accuracy, precision, confounder influence, and variability were investigated using scaled median symmetric accuracy (ζ), thus finding excellent accuracy (mean ζ = 0.99%). Although significant, no relevant confounders were found (mean ζ ± SD circles = 0.69% ± 0.68% vs. triangles = 1.3% ± 0.62%). Analysis of 181 literature peak plasma concentration values revealed a considerable discrepancy between reported and post hoc digitized data with 85% having ζ > 5%. Our findings suggest that data digitizing is precise and important. However, because the greatest pitfall comes from pre‐existing errors, we recommend always making published data available as raw values.

Purpose Characterize the pharmacokinetics of oral crizotinib in children with cancer. Methods Sixty-four children with solid tumors or anaplastic large-cell lymphoma (ALCL) enrolled on a phase 1/2 trial of the ALK, MET and ROS1 inhibitor, crizotinib, had pharmacokinetic sampling after the first dose (n = 15) or at steady state (n = 49). Dose levels studied were 100, 130, 165, 215, 280 and 365 mg/m2/dose administered twice daily. Two capsule and two oral liquid formulations were used over the course of the trial. Crizotinib was quantified with a validated HPLC/tandem mass spectrometry method with a lower limit of detection of 0.2 ng/mL. Pharmacokinetic parameters were derived using non-compartmental analysis. Results Time to peak plasma concentration was 4 h. At 280 mg/m2 (MTD), mean (±SD) steady-state peak plasma concentration was 717 ± 201 ng/mL, and steady-state trough plasma concentration was 480 ± 176 ng/mL. At steady state, AUC0–τ was proportional to dose over the dose range of 215–365 mg/m2/dose. Apparent clearance of crizotinib was 731 ± 241 mL/min/m2. Steady-state AUC0–τ at 280 mg/m2/dose was 2.5-fold higher than the AUC0–∞ in adults receiving 250 mg (~140 mg/m2). Age, sex and drug formulation do not account for the inter-subject variability in AUC0–τ at steady state. The accumulation index was 4.9, and the half-life estimated from the accumulation index was 36 h. Conclusions The pharmacokinetics of oral crizotinib in children is similar to that in adults. Steady-state trough-free crizotinib concentrations in plasma at the MTD exceed inhibitory concentrations of crizotinib in ALCL cell lines. ClinicalTrials.gov identifier NCT00939770.

The determination of alendronate (ALE) in biofluids using a low-cost instrument is potentially useful in preclinical pharmacokinetic studies. This study developed and validated a high-performance liquid chromatography with ultraviolet method for ALE determination in rat plasma using precolumn derivatization with phenyl isothiocyanate (PITC). Inhibiting compounds in the samples were first eliminated using solid-phase extraction. ALE in the sample was subsequently allowed to react with PITC to form a phenylthiocarbamoyl derivative for further analysis. The assay was linear within the concentration range of 0.29–25.0 µg/mL. The precision and accuracy were less than 3.9% and 98.0 ± 3.9%, respectively. The limits of detection and quantification were 0.08 and 0.20 µg/mL, respectively. The method was successfully used to evaluate the pharmacokinetic parameters of ALE in rats following a single oral administration (30.0 mg/kg). The results show that the peak plasma ALE concentration is 0.69 ± 0.18 µg/mL. ...

Background Over the past few years, several drugs, each with a different mechanism, have been developed for the treatment of pulmonary hypertension (PH) and are now prescribed in the clinical setting. While the optimal doses of these drugs in adults have been determined, the optimal dose in children, however, is unclear. The aim of this study was therefore, to measure blood drug levels and analyze the pharmacokinetics of two such drugs in children. Methods From April 2010 to May 2015, we prospectively enrolled 23 children with PH for treatment with bosentan and/or tadalafil. Twenty children were treated with bosentan and 19 received tadalafil. Sixteen children were given both drugs. Blood samples were collected after 2 weeks of treatment, and blood drug levels measured using high-performance liquid chromatography. Results For both drugs, the peak plasma concentration was lower and the half-life was shorter than the known values in adults. The blood trough level of bosentan significantly correlated with its dose, but no such correlation was seen for tadalafil. For both drugs, no correlation was observed between age and blood drug levels. Conclusions Oral dosing with bosentan and tadalafil in children may not achieve therapeutic blood concentration. Thus, the optimal dosing must be established individually while monitoring blood drug level.

Emily K Cook,Nana Satake,Ben W Sykes,Emma L Bennett,Paul C Mills School of Veterinary Sciences, The University of Queensland, Gatton, Queensland, Australia Abstract: Investigation into the pharmacokinetic profile of esomeprazole was conducted using eight healthy dogs after intravenous (IV) and oral (po) administration in a two-part randomized crossover study. The dogs were fasted for a minimum of 12 hours and then received esomeprazole either intravenously (dose range 0.93–1.48 mg/kg) or orally using an enteric-coated formulation (dose range 0.95–1.50 mg/kg). After a 1-week washout period, the dogs received an alternative treatment. Serial blood samples were collected at predetermined time points, and plasma esomeprazole concentrations were determined by using ultra-high-performance liquid chromatography–mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Then, the area under the plasma concentration/time curve (AUC) and maximal plasma concentration (Cmax) values were normalized to a 1.0 mg/kg dose of esomeprazole, that is, AUC/dose. Median (range) dose-normalized peak plasma concentration (Cmax) values for the IV and po formulations were 4.06 µg/mL (2.47–4.57 µg/mL) and 1.04 µg/mL (0.31–1.91µg/mL), respectively. The median (range) time-to-peak concentration (Tmax) for the po formulation was 105 minutes (45–360 minutes). Median (range) plasma terminal half-life (t½) was 45.56 minutes (39.43–64.20 minutes) for the IV formulation and 63.97 minutes (44.02–109.94 minutes) for the enteric-coated po formulation. The median (range) po bioavailability was 63.33% (32.26%–79.77%). Clinically, both po and IV formulations were well tolerated with minimal side effects observed. Keywords: proton pump inhibitors, gastric ulcers, and oesophagitis

Fiasp® (insulin aspart, Novo Nordisk) is a faster-acting injectable insulin formulation that is administered subcutaneously (SC) for blood glucose management. We hypothesized that intradermal (ID) administration could improve the pharmacokinetic profile of Fiasp® when compared to traditional SC injection. Herein, we describe a simple, scalable and cost-effective hollow microneedle platform to evaluate the effects of ID administration on Fiasp® pharmacokinetics. Three groups of 8 rats received 1 IU/kg by SC injection or by ID injection using either a single or quadruple microneedle projection design. Blood was collected from 5-240 mins post-injection and assayed for insulin (ELISA, Crystal Chem) and blood glucose (hand-held glucometer) concentrations. The results (below) show that plasma insulin levels were comparable for all groups with mean values ranging from 464 to 480 µU/mL. Yet, the peak plasma concentrations were 1.5-3-fold earlier for rats treated using the microneedle designs. This preliminary data suggests that ID injection of Fiasp® using these novel hollow microneedle designs results in faster absorption and thereby could lead to a more rapid onset of action. Disclosure S. Ranamukha: None. I. Mansoor: Stock/Shareholder; Self; Microdermics. K. Feng: Employee; Self; Microdermics Inc. B. Stoeber: Other Relationship; Self; Microdermics Inc.. M. Wehbe: None. R. St Clair: Employee; Self; Microdermics Inc. C. Piche: Employee; Self; Locemia Solutions. Stock/Shareholder; Self; Locemia Solutions. Consultant; Self; Microdermics Inc. Stock/Shareholder; Self; Diasome Pharmaceuticals, Inc., Bigfoot Biomedical. J. Moreau: Consultant; Self; Microdermics.

Background Cyclosporine A (CyA) is a drug for moderate-to-severe psoriasis. Recently, a generic formulation has been approved as bioequivalent to the branded one. The guidelines for the bioequivalence for critical-dose drugs with a narrow therapeutic range, such as CyA, are questionable. Therefore, it is important to assess the clinical outcome and the pharmacokinetics of different formulations in various patient groups. The current literature lacks of this information in dermatology. The primary objective of this prospective study is to investigate the clinical equivalence (in terms of maintenance of clinical effect) between the generic formulation of CyA and its branded one in patients with psoriasis. A secondary objective is to analyze their trough (C 0 ) and peak levels (C 2 ). Methods Twenty patients with stable psoriasis under treatment with the branded CyA were monitored in terms of clinical efficacy (psoriasis area severity index, PASI), safety (laboratory values), and their pharmacokinetics utilizing trough (C 0 ) and peak plasma concentration (C 2 ). The same patients were subsequently shifted to the generic formulation for comparison. Results In our sample the efficacy of the two formulations was equal in most cases (P=0.863). A non-significant difference between the C 0 and C 2 of the branded CyA compared to the generic one emerged (respectively P=0.738 and P=0.695). Conclusions The branded and the generic formulations of CyA seem to be not only bioequivalent, but also comparable in terms of clinical efficacy in patients with psoriasis. However, larger samples are required to confirm these findings.

The herb-derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral (p.o.) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, p.o.), glycyrrhizin (15 mg/kg, intraperitoneal [i.p.]), or oxymatrine (60 mg/kg, p.o.). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration-time curve (AUC0-t ) and the peak plasma concentration (Cmax ) of ribavirin and ribavirin base by 31.2-44.5% and 48.9-50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0-t of both ribavirin and its metabolite by 35.3-37.6% and 38.6-39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and Cmax . Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine.

To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5 mg/kg bodyweight.Five healthy Saanen goats, aged 12-14 months and weighing 35-40 kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5 mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group.Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (p0.05). The terminal half-life was longer (15.16 (SD 4.74) vs. 10.69 (SD 1.49) hours) and the MRT was shorter (15.67 (SD 2.37) vs. 24.33 (SD 3.12) hours) following S/C than oral administration (p0.05), but bioavailability was similar (98.24 (SD 9.62) vs. 96.49 (SD 10.71)%).Subcutaneous administration of meloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.

The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC–MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0–t) values ranged from 1.75 to 11.80 (mg·h/L). J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688., Graphical abstract A simple, selective, and sensitive LC–MS method was developed and validated. Pharmacokinetic study of gallocatechin-7-gallate (J10688) in rats was carried out. The pharmacokinetic properties of J10688 in SD rats were characterized as quick distribution and clearance. fx1

Present study efforts are focusing to develop the flurbiprofen fast dissolving tablets using sublimation method to enhance the dissolution rate. In this study an attempt was made to fasten the drug release from the oral tablets by incorporating the sublimating agents in the presence of crosspovidone as superdisintegrant and studied the effect on dissolution rate when compared to conventional tablets. In the present study, sublimated fast dissolving tablets were prepared by direct compression method. The prepared tablets were characterized for physical parameters and drug release behavior and the best formulation was subjected to pharmacokinetic studies. From in vitro drug release studies, the formulation F2 showed fast drug release of about 99.94±0.26% in 30 min, and disintegration time 34.42 ± 0.74 sec. The percent drug release in 15 min (Q15) and initial dissolution rate for formulation F2 was 91.46±1.42%, 6.10%/min. The dissolution efficiency was found to be 53.44 and it is increased by 4.5 fold with F2 sublimated tablets. From the pharmacokinetic evaluation, the conventional tablets producing peak plasma concentration (Cmax) was 9023.68±561.83 ng/ml at 3 h Tmax and F2 sublimated tablets showed Cmax 11126.71±123.56 ng/ml at 2 h Tmax. The area under the curve for the conventional and F2 tablets was 30968.42±541.52 and 42973.66±568.13 ng h/ml. Hence, the development of flurbiprofen fast dissolving tablets by sublimation method is a right way to enhance not only the dissolution rate but also the absorption rate.

Objective: Compare the pharmacokinetics of atropine administered via the intravenous (IV), intramuscular (IM), and intraosseous (IO) routes in a normovolemic and hypovolemic swine model. Design: Prospective, between subjects, experimental study. Setting: Vivarium. Subjects: Yorkshire-cross swine (N = 36). Intervention: Atropine was administered via IV, IM, or IO routes to normovolemic and hypovolemic swine. Blood samples were drawn at regular intervals after atropine administration and analyzed for plasma atropine concentration. Pharmacokinetic parameters were obtained from modeling the plasma concentrations. Main outcome measurements: Pharmacokinetic parameters, maximum concentration (C max ) and time to maximum concentration (T max ). Results: The IV and IO groups in both the normovolemic and hypovolemic models reached peak plasma concentration immediately and had a very rapid distribution phase with no apparent absorption phase for the IO groups. Peak plasma concentration and time to reach peak concentration were both significantly lower for the IM groups. There was a significant increase in absorption time with IM administration in the hypovolemic model compared to the normovolemic model. Conclusion: The IO route is an effective method of administering atropine and is comparable to the IV route even under conditions of significant hemorrhage. Therapeutic levels of atropine may be delayed and possibly difficult to obtain via IM injection in the presence of hypovolemic shock.