Dependence of Bioavailability on Mean Absorption Time: What Does It Tell Us?

AbstractThe extent and rate of bioavailability are fundamental measures to characterize the pharmacokinetics of drugs after oral administration. Together with bioavailability (F), the mean absorption time (MAT) can be used to define the rate of bioavailability, i.e., the rate of drug absorption. Previous results suggest thatF may depend onMAT. Estimates ofF andMAT were obtained from the input function (sum of two inverse Gaussian functions) used to model the oral absorption process. The estimation was performed by population analysis (nonlinear mixed-effects modeling) based on data from bioavailability studies in healthy volunteers. For trospium and ketamine, F decreased significantly with increasingMAT, while for propiverine, a significant increase was observed. Thus, the interindividual variability inF could be largely attributed to the interindividual variability inMAT. For trospium and propiverine, the relative dispersion (normalized variance) of the absorption time distribution increased significantly withMAT. For trospium and propiverine, the plot ofF versusMAT provides information about the effect of gastrointestinal transit on drug absorption. In contrast, an increase in hepatic extraction with increasingMAT is responsible for the dependence ofF onMAT. TheF versusMAT plot is suggested as a simple diagnostic tool in evaluating the results of bioavailability studies.Graphical Abstract
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research