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Updated: Aug 27, 2025

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Analysis of Complex Absorption After Multiple Dosing: Application to the Interaction Between the P-glycoprotein
Michael Weiss1, David Z D'Argenio2, Werner Siegmund3
1Department of Pharmacology, Martin Luther University Halle-Wittenberg, Halle, Germany. michael.weiss@medizin.uni-halle.de.
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.
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