A Microdose Cocktail to Evaluate Drug Interactions in Patients with Renal Impairment.

Renal impairment (RI) is known to influence the pharmacokinetics of nonrenally eliminated drugs, although the mechanism and clinical impact is poorly understood. We assessed the impact of RI and single dose oral rifampin (RIF) on the pharmacokinetics of CYP3A, OATP1B, P-gp, and BCRP substrates using a microdose cocktail and OATP1B endogenous biomarkers. RI alone had no impact on midazolam (MDZ), maximum plasma concentration (C ), and area under the curve (AUC), but a progressive increase in AUC with RI severity for dabigatran (DABI), and up to ~2-fold higher AUC for pitavastatin (PTV), rosuvastatin (RSV), and atorvastatin (ATV) for all degrees of RI was observed.

Steady-state bioavailability of prescription omega-3 on a low-fat diet is significantly improved with a free fatty acid formulation compared with an ethyl ester formulation: the ECLIPSE II study.

The systemic bioavailability of free fatty acid (FFA) forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with ethyl ester (EE) forms is dependent on the presence of intestinal lipases and is highest during consumption of high-fat meals. Given that patients with cardiovascular disease are advised to reduce dietary fat intake, potentially lowering the bioavailability and therapeutic benefit, the hypothesis that FFA forms provide for higher bioavailability compared with EE forms under low-fat diet conditions was tested where the pharmacokinetics of the FFA form (Epanova™) were compared with those of an ethyl ester form (Lovaza®) following repeat dosing. Fifty-two healthy male and female subjects were equally allocated to one of two open-label, parallel-group cohorts.

Pharmacokinetic studies in women of 2 novel oral formulations of tranexamic acid therapy for heavy menstrual bleeding.

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.

Thorough cardiac QTc interval conductance assessment of a novel oral tranexamic acid treatment for heavy menstrual bleeding.

Objective: To assess the effect of a novel oral tranexamic acid treatment on cardiac repolarization in a randomized, double-blind, positive- and placebo-controlled, four-treatment single-dose cross-over inpatient study.

Methods: QTc interval and drug exposure relationship analyses were performed using triplicate digital electrocardiographs (ECGs) collected from 12-lead Holter monitors from healthy females (n = 48) with plasma drug concentrations and pharmacokinetics simultaneously evaluated over 24 h post-dose. Therapeutic (1.