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Modeling the Kinetics of Digoxin Absorption: Enhancement by P‐Glycoprotein Inhibition
Author(s) -
Weiss Michael,
Sermsappasuk Pakawadee,
Siegmund Werner
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010396711
Subject(s) - digoxin , kinetics , p glycoprotein , pharmacology , chemistry , pharmacokinetics , absorption (acoustics) , glycoprotein , medicine , materials science , biochemistry , physics , heart failure , composite material , multiple drug resistance , antibiotics , quantum mechanics
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.