PT  - JOURNAL ARTICLE
AU  - David R. Taft
AU  - Ganesh R. Iyer
AU  - Leon Behar
AU  - Robert V. Digregorio
TI  - Application of a First-Pass Effect Model to Characterize the Pharmacokinetic Disposition of Venlafaxine after Oral Administration to Human Subjects
DP  - 1997 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1215--1218
VI  - 25
IP  - 10
4099  - http://dmd.aspetjournals.org/content/25/10/1215.short
4100  - http://dmd.aspetjournals.org/content/25/10/1215.full
SO  - Drug Metab Dispos1997 Oct 01; 25
AB  - Venlafaxine (VEN), a drug used in the treatment of depression, undergoes significant first-pass metabolism after oral dosing toO-desmethylvenlafaxine (ODV), a metabolite with comparable therapeutic activity to that of parent drug. The pharmacokinetic disposition of VEN was characterized using a “first-pass” model that incorporates a presystemic compartment (liver) to account for the first-pass metabolism of VEN to ODV. A series of differential equations were simultaneously fitted to plasma concentrations of parent and metabolite. A good fit of the model to observed data was demonstrated, generating estimates for the following parameters:ka (1.31 ± 0.009 hr−1),VVEN (252 ± 87.6 liters),CLint (65.8 ± 39.7 liters/hr),RL (liver:plasma partition coefficient, 29.6 ± 18.3), VODV (181 ± 84.1 liters), and CLODV (23.5 ± 12.5 liters/hr). Parameter estimates correlated closely with those obtained through noncompartmental methods. These results indicate that the time-course disposition of a compound undergoing first-pass hepatic metabolism after oral dosing can be successfully modeled. The American Society for Pharmacology and Experimental Therapeutics