Michael Weiss1, David Z D'Argenio2, Werner Siegmund3. 1. Department of Pharmacology, Martin Luther University Halle-Wittenberg, Halle, Germany. michael.weiss@medizin.uni-halle.de. 2. Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. 3. Department of Clinical Pharmacology, Center of Drug Absorption and Transport (C_DAT), University Medicine Greifswald, Greifswald, Germany.
Abstract
PURPOSE: In order to clarify the effect of rifampicin on the bioavailability of the P-glycoprotein substrate talinolol, its absorption kinetics was modeled after multiple-dose oral administration of talinolol in healthy subjects. METHODS: A sum of two inverse Gaussian functions was used to calculate the time course of the input rate into the systemic circulation. RESULTS: The estimated rate of drug entry into the systemic circulation revealed two distinct peaks at 1 and 3.5 h after administration. Rifampicin did not affect bioavailability of talinolol, but did shift the second peak of the input function by 1.3 h to later times. Elimination clearance and one of the intercompartmental distribution clearances increased significantly under rifampicin treatment. CONCLUSIONS: Rifampicin changes the time course of absorption rate but not the fraction absorbed of talinolol. The model suggests the existence of two intestinal absorption windows for talinolol.
PURPOSE: In order to clarify the effect of rifampicin on the bioavailability of the P-glycoprotein substrate talinolol, its absorption kinetics was modeled after multiple-dose oral administration of talinolol in healthy subjects. METHODS: A sum of two inverse Gaussian functions was used to calculate the time course of the input rate into the systemic circulation. RESULTS: The estimated rate of drug entry into the systemic circulation revealed two distinct peaks at 1 and 3.5 h after administration. Rifampicin did not affect bioavailability of talinolol, but did shift the second peak of the input function by 1.3 h to later times. Elimination clearance and one of the intercompartmental distribution clearances increased significantly under rifampicin treatment. CONCLUSIONS: Rifampicin changes the time course of absorption rate but not the fraction absorbed of talinolol. The model suggests the existence of two intestinal absorption windows for talinolol.
Authors: Felicitas Stoll; Antje Blank; Gerd Mikus; David Czock; Kathrin I Foerster; Simon Hermann; Katja Gümüs; Amin Muhareb; Simone Hummler; Max Sauter; Johanna Weiss; Jürgen Burhenne; Walter E Haefeli Journal: Clin Pharmacol Drug Dev Date: 2021-07-15