Effect of Food Intake on the Pharmacokinetics of the Selective Progesterone Receptor Modulator Vilaprisan: A Randomized Clinical Study in Healthy Postmenopausal Women

Abstract

This exploratory, open-label, randomized, 3-period crossover study in 12 healthy postmenopausal women investigated the effects of food intake on the pharmacokinetics of vilaprisan. Single doses of vilaprisan (2 mg) were administered under fasting conditions, after intake of a high-fat, high-calorie meal, and after intake of a moderate-fat, moderate-calorie meal. The intake of food had only a marginal impact on the oral bioavailability of vilaprisan. The mean exposure of vilaprisan (area under the plasma concentration-time curve [AUC]) was increased by approximately 20% when the drug was taken after a meal and not on an empty stomach (point estimate for AUC ratios [%] and 90% confidence interval: high-fat and-calorie meal/fasting 121 [114-128]; moderate-fat and-calorie meal/fasting 118 [111-125]). The rate of absorption was slightly decreased when the drug was taken after a meal as indicated by approximately 10% lower mean maximum concentrations (C max) of vilaprisan in plasma (C max ratios: high-fat and-calorie meal/fasting 87.9 [75.6-102]; moderate-fat and-calorie meal/fasting 89.4 [76.9-104]) and a prolonged time to C max (fasting: 1.5 hours; fed conditions; ∼4 hours). Overall, the results of this study indicate that vilaprisan can be administered equally well with or without food.

Clinical Pharmacokinetics and Pharmacodynamics of the Selective Progesterone Receptor Modulator Vilaprisan: A Comprehensive Overview

“…After oral administration in the form of immediate-release tablets, vilaprisan is rapidly and almost completely absorbed, with times to maximum observed plasma concentrations (C max ) between 1 and 2 h after single-dose administration [11,12]. Food intake, as shown below, has a negligible impact on the PK of vilaprisan [13]. The systemic exposure of vilaprisan, expressed as area under the plasma concentration-time curve from time zero to infinity (AUC) after single-dose administration, or to 24 h after multiple-dose administration (AUC 24md ), increases approximately dose-proportionally in the dose range 1-30 mg.…”

“…Food intake has a negligible impact on the PK of vilaprisan. In a food-drug interaction study [13], the extent of absorption (as reflected in the AUC) was increased by approximately 20% when vilaprisan was taken at the end of a high-fat/high-calorie or moderate-fat/moderate-calorie meal compared with fasted conditions. On the other hand, the rate of absorption was slightly decreased (C max reduced by approximately 10%) and the time to C max increased from 1.5 to 4 h. These differences are not clinically relevant and thus no specific recommendations on whether to take vilaprisan on an empty stomach or with a meal are required.…”

“…No dose adjustment is required in patients with mild or moderate hepatic impairment. Use of VPR in patients with severe hepatic impairment is not AUC was slightly increased in the fed vs. fasted state (+ 20%) and C max was slightly reduced (− 11%)[13]. This difference is not clinically relevant and no specific recommendations on how to take VPR (i.e., with or…”