title: Modeling the kinetics of digoxin absorption: enhancement by P-glycoprotein inhibition.
abstract: An increase in the area under the curve (AUC) after oral digoxin due to coadministration of drugs known as P-glycoprotein (P-gp) inhibitors has been reported in several studies, but there is very little information on the rate of absorption after P-gp inhibition. Based on an inverse Gaussian density absorption model and using a population approach, the authors reanalyzed data showing an increase in oral digoxin AUC in healthy volunteers after coadministration of talinolol. The model fitted the data well, and the results revealed that the maximum rate of digoxin absorption increased nearly 2-fold, whereas bioavailability increased only by 21%. It is concluded that the increase in the rate of absorption seems to be a better indicator of intestinal P-gp inhibition than the increase in extent of absorption. Furthermore, the authors use a simulation study to demonstrate the ability of the method to estimate bioavailability based on the population characteristics of digoxin disposition kinetics obtained from a different group of healthy volunteers.
authors.affiliation: Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand. michael.weiss@medizin.uni-halle.de
authors.forename: Michael
authors.initials: M
authors.lastname: Weiss
authors.forename: Pakawadee
authors.initials: P
authors.lastname: Sermsappasuk
authors.forename: Werner
authors.initials: W
authors.lastname: Siegmund
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000042:Absorption; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology*; D003198:Computer Simulation; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D008954:Models, Biological; D016011:Normal Distribution; D011412:Propanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D011412:Propanolamines; C011550:talinolol; D004077:Digoxin