Pharmacokinetic Interaction between Faldaprevir and Cyclosporine or Tacrolimus in Healthy Volunteers: A Prospective, Open-Label, Fixed-Sequence, Crossover Study.

Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus. In this single-centre, open-label, fixed-sequence, crossover study of 32 healthy adult male and female volunteers, subjects received either a single dose of cyclosporine (CsA) 50 mg (N = 16) or tacrolimus (TAC) 0.5 mg (N = 16), followed by a washout of at least 14 days.

Contribution of Major Metabolites toward Complex Drug-Drug Interactions of Deleobuvir: In Vitro Predictions and In Vivo Outcomes.

The drug-drug interaction (DDI) potential of deleobuvir, an hepatitis C virus (HCV) polymerase inhibitor, and its two major metabolites, CD 6168 (formed via reduction by gut bacteria) and deleobuvir-acyl glucuronide (AG), was assessed in vitro. Area-under-the-curve (AUC) ratios (AUCi/AUC) were predicted using a static model and compared with actual AUC ratios for probe substrates in a P450 cocktail of caffeine (CYP1A2), tolbutamide (CYP2C9), and midazolam (CYP3A4), administered before and after 8 days of deleobuvir administration to HCV-infected patients. In vitro studies assessed inhibition, inactivation and induction of P450s.

Mass balance, metabolite profile, and in vitro-in vivo comparison of clearance pathways of deleobuvir, a hepatitis C virus polymerase inhibitor.

The pharmacokinetics, mass balance, and metabolism of deleobuvir, a hepatitis C virus (HCV) polymerase inhibitor, were assessed in healthy subjects following a single oral dose of 800 mg of [(14)C]deleobuvir (100 μCi). The overall recovery of radioactivity was 95.2%, with 95.

The challenges and realties of diaper area cleansing for parents.

Objective: To explore the complexities of diaper area cleansing reported by women participating in a randomized controlled trial designed to compare optimally formulated baby wipes (Johnson's Baby Skincare fragrance free wipe) with cotton wool and water.

Design: A mixed-method design incorporating quantitative and qualitative methods to explore maternal views and experiences of using baby wipes or cotton wool and water to cleanse their newborn's diaper area over an 8-week period.

Setting: Participants were recruited from a large regional maternity hospital in Northern England.

Pharmacokinetics of BILR 355 after multiple oral doses coadministered with a low dose of ritonavir.

The pharmacokinetics and safety of BILR 355 following oral repeated dosing coadministered with low doses of ritonavir (RTV) were investigated in 12 cohorts of healthy male volunteers with a ratio of 6 to 2 for BILR 355 versus the placebo. BILR 355 was given once a day (QD) coadministered with 100 mg RTV (BILR 355/r) at 5 to 50 mg in a polyethylene glycol solution or at 50 to 250 mg as tablets. BILR 355 tablets were also dosed at 150 mg twice a day (BID) coadministered with 100 mg RTV QD or BID.

Quantitation of five nevirapine oxidative metabolites in human plasma using liquid chromatography-tandem mass spectrometry.

A multiple-reaction-monitoring LC/MS/MS method for the analysis of nevirapine oxidative metabolites, 2-hydroxynevirapine, 3-hydroxynevirapine, 8-hydroxynevirapine, 12-hydroxynevirapine, and 4-carboxynevirapine, in human plasma was developed and validated. The metabolites were isolated from 50 microL heparinized plasma by enzymatic hydrolysis of the glucuronide conjugates to the free metabolite followed by protein precipitation with acetonitrile. Peaks were quantitated at 3.