Pharmacokinetic and Bioequivalence Evaluation of Ulipristal Acetate in Healthy Chinese Subjects in the Fasting and Postprandial Conditions.

Abstract

Ulipristal acetate (UPA) is indicated for the treatment of moderate to severe uterine fibroids in adult women of reproductive age who are candidates for surgical intervention. A single-center, randomized, open-label, 2-period crossover study was conducted in 46 healthy female subjects under both fasting and postprandial conditions. Blood samples were collected for pharmacokinetic analysis following the oral administration of a 5-mg dose of UPA. Plasma concentrations were quantified using liquid chromatography-tandem mass spectrometry. The 90% confidence intervals of the ratio of geometric mean of maximum concentration, area under the plasma concentration-time curve (AUC) from time 0 to the time of last measurable concentration, AUC from time 0 to infinity of UPA, and monodemethyl-UPA all fell within the bioequivalence range of 80%-125% under both fasting and postprandial conditions. In this study, coadministration oral UPA 5 mg with a high-fat meal resulted in a maximum concentration that was approximately 25% lower, a delayed time to reach maximum concentration (from a median of 0.5-3 hours) than with the fasting state, and an AUC from time 0 to infinity that increased by a factor of 1.58-1.85. Similar results were observed for the active metabolite (monodemethyl-UPA). All adverse events recorded during the study were of mild intensity, and no serious adverse events were observed. Both preparations showed good safety and tolerability. No data are available on the clinical importance of the food effect. Until such data becomes available, treating physicians should be aware of the increase in systemic exposure based on fasting versus postprandial conditions and plan dosage regimens accordingly.