These results suggest that pomelo juice increases the bioavailability of cyclosporine, possibly by inhibiting CYP3A or P-gp activity (or both) in the gut wall. However, drinking a glass of cranberry juice does not appear to significantly influence the disposition of cyclosporine.

The World One Health Congresses are biennial gatherings of approximately 1500 professionals from relevant international organisations, OIE, FAO, WHO, World Bank, leading scientific experts and researchers in the field of One Health, animal production and trade, food safety, animal health, human health and environmentology/ecology, government representatives in public health, human health, food safety, environmental health and global health security. The Congress is organized by the One Health Platform. This white paper summarizes highlights of the 5th International One Health Congress in Saskatoon, Canada, June 2018 and serves as a roadmap for the future, detailing several concrete action points to be carried out in the runup to the 6th World One Health Congress in Edinburgh, Scotland, June 2020.

A novel transdermal formulation of fentanyl-containing dipropylene glycol droplets dispersed in a silicone matrix with a rate-controlling membrane was developed. Healthy male subjects (n = 24) received repeated 72-hour applications of fentanyl (50 mug/h) as the novel matrix and the conventional reservoir formulations in a randomized, 2-way crossover study. Blood samples were collected, and serum concentrations of fentanyl were assayed using liquid chromatography with mass spectrometry detection. The mean area under the curve (AUCtau) and peak concentrations (C(max)) of the matrix formulation were 84 838 pg.h/mL and 1680 pg/mL, respectively. Ratio and 90% confidence intervals of AUCtau and C(max) between the 2 formulations were within 80% to 125%. Adherence of the matrix formulation was higher than the reservoir formulation (62.5 vs 56.2%, P < .0001), without affecting skin irritation. Vital signs and adverse events of the 2 formulations were similar in nature and frequency. The novel matrix formulation displayed enhanced adherence and resulted in similar pharmacokinetics and tolerability as the reservoir formulation.

This randomized, open-label, crossover study investigated the influence of food on the pharmacokinetics of extended-release hydromorphone in 30 healthy volunteers. Participants received extended-release hydromorphone 16 mg in the fasted state and immediately after a high-fat breakfast. In addition, the pharmacokinetics of a 16-mg dose of extended-release hydromorphone and a 16-mg daily dose (4 mg qid) of immediate-release hydromorphone in the fasted state were compared. Treatments were separated by washout periods of 7 to 14 days. Naltrexone was given throughout each treatment period to block the opioid effects of hydromorphone. The 90% confidence intervals (CIs) of the ratios of geometric means for maximum plasma concentrations (C(max)) and area under the plasma concentration-time curve (AUC) for extended-release hydromorphone in the fed and fasted states were within the bioequivalence criteria range of 80% to 125%. In the fasted state, the 90% CIs of the ratios of AUC geometric means for extended-release hydromorphone and immediate-release hydromorphone were also within the bioequivalence range. Both hydromorphone treatments were well tolerated. This study shows that the bioavailability of extended-release hydromorphone is not affected by food and that the bioavailability of extended-release hydromorphone under fasting conditions is comparable with that of the immediate-release formulation when administered at the same total daily dose.

Two randomized, open-label clinical studies involving healthy female volunteers aged 18-45 years (study 1, N = 32; study 2, N = 40) are described, which characterize the pharmacokinetics and steady-state dosage regimen performance of 2 novel, modified-release tranexamic acid tablet formulations. The objective of these studies was to identify the optimum product formulation to advance into late-phase clinical trials for heavy menstrual bleeding. For study 1, participants received single 1.3-g doses (2 650-mg tablets) of tranexamic acid modified-immediate-release (MIR) and tranexamic acid delayed-release (DR) formulations under fasting conditions compared with nonfasting conditions (after breakfast). For study 2, participants received tranexamic acid MIR or tranexamic acid DR as a single 1.3-g dose followed by a dosage regimen of 1.3 g every 8 hours for 5 days. Plasma tranexamic acid concentrations reached minimum effective levels (≥5 μg/mL) within 1.5 hours and within 3 hours after a 1.3-g tranexamic acid MIR and tranexamic acid DR dose, respectively. Food did not appreciably influence tranexamic acid MIR pharmacokinetics, whereas a high-fat meal significantly lowered the maximum concentration produced with tranexamic acid DR. Peak systemic exposure and maintenance of plasma tranexamic acid concentrations within the therapeutic range (5-15 μg/mL) were optimally achieved with 1.3 g of the MIR formulation dosed every 8 hours. The MIR and DR formulations were well tolerated. Peak-to-trough steady-state performance of the tranexamic acid MIR 1.3-g product (dosed every 8 hours, or 3 times daily, for up to 5 days) supported its advancement to late-phase clinical trials in women with heavy menstrual bleeding.

SUMMARY BackgroundNovel rabeprazole extended-release (ER) formulations were developed to provide prolonged gastric acid suppression and potentially improved clinical outcomes in GERD patients.

The pharmacokinetics of 150 mg lamivudine, 300 mg zidovudine, and 200 mg nevirapine were assessed following single oral administration of a fixed-dose combination tablet and coadministration of the separate innovator products in healthy male subjects (n = 64) under fasting conditions in an open-label, randomized, 2-way crossover study. Multiple blood samples were collected up to 72 hours and plasma concentrations of antiretrovirals were assayed using liquid chromatography/tandem mass spectrometry methods. Pharmacokinetic parameters were calculated using noncompartmental methods, and bioequivalence was assessed using an analysis of variance model. The ratio of the least squares mean (fixed-dose combination to individual products) and 90% confidence intervals of AUC(0-t), AUC(0-infinity), and C(max) for lamivudine, zidovudine, and nevirapine were all within 80.0% to 125.0%, suggesting a similar rate and extent of antiretroviral exposure in the bloodstream. Mean oral clearance (CL/F) values of lamivudine, zidovudine, and nevirapine for the fixed-dose combination were 23.7, 127, and 1.65 L/h, respectively. The fixed-dose combination and individual products were equally safe and well tolerated, with only a few subjects experiencing drug-related adverse events. The current fixed-dose combination of lamivudine, zidovudine, and nevirapine is expected to provide a similar efficacy/safety profile as coadministration of the individual products, a better adherence to treatment, and considerable cost savings in the treatment of HIV.

AimTo determine the pharmacokinetics, safety and performance of a novel matrix formulation of fentanyl. MethodsTransdermal fentanyl was administered as the novel matrix and the Durogesic ® reservoir formulations (24 subjects, 100 µ g h − 1 ) in a randomized, fully replicate, fourway crossover study. Serum concentrations of fentanyl were assayed by LC/MS/MS. Pharmacokinetic parameters of fentanyl and performance (adherence and skin irritability) were evaluated. ResultsTest/reference ratio (90% confidence intervals) for AUC 0-t , AUC inf and C max were 105.5% (99.4, 112.0), 105.3% (99.3, 111.6) and 111.4% (100.4, 123.6), respectively. Adherence and skin irritability results of the two formulations were similar. ConclusionThe two formulations are expected to result in similar efficacy for the management of severe pain.