CYP3A4-mediated effects of rifampicin on the pharmacokinetics of vilaprisan and its UGT1A1-mediated effects on bilirubin glucuronidation in humans

British Journal of Clinical Pharmacology
Niladri ChattopadhyayMarcus-Hillert Schultze-Mosgau

Abstract

The primary aim of the present study was to quantify the effects of rifampicin, a strong cytochrome P450 (CYP) 3A4 inducer, on the pharmacokinetics of the new selective progesterone receptor modulator, vilaprisan. In addition, the effects of rifampicin on the glucuronidation of bilirubin, an endogenous UDP-glucuronosyltransferase family 1 member A1 (UGT1A1) substrate, were explored. This was an open-label, two-period study in 12 healthy postmenopausal women. Subjects received a single oral dose of vilaprisan 4 mg in each period. In period 2, administration of vilaprisan was preceded and followed by rifampicin 600 mg day-1 . A subtherapeutic dose of midazolam (1 mg) was coadministered with vilaprisan to monitor CYP3A4 induction. Details of the administration and sampling schedule were optimized by means of a physiologically based pharmacokinetic model. Plasma concentrations of vilaprisan, midazolam, and 1'- hydroxy-midazolam were measured and rifampicin-associated changes in the glucuronidation of bilirubin were determined. As predicted by our model, the coadministration of rifampicin was associated with a substantial decrease in exposure to vilaprisan and midazolam - indicated by the following point estimates (90% confidence in...Continue Reading

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Citations

May 22, 2019·British Journal of Clinical Pharmacology·Niladri ChattopadhyayMarcus-Hillert Schultze-Mosgau
Jul 28, 2020·Clinical Pharmacology in Drug Development·Hongzhong LiuMarcus-Hillert Schultze-Mosgau
Oct 13, 2021·European Journal of Drug Metabolism and Pharmacokinetics·Marcus-Hillert Schultze-MosgauMasato Kaneko

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