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Food did not affect the bioavailability of venlafaxine or its active metabolite, ODV. Time of administration (AM vs PM) did not affect the pharmacokinetics of venlafaxine and ODV from the 75 mg Effexor XR capsule. Metabolism and Excretion Following absorption, venlafaxine undergoes extensive presystemic metabolism in the liver, primarily to ODV, but also to N-desmethylvenlafaxine, N, O-didesmethylvenlafaxine, and other minor metabolites. In vitro studies indicate that the formation of ODV is catalyzed by CYP2D6; this has been confirmed in a clinical study showing that patients with low CYP2D6 levels (" poor metabolizers") had increased levels of venlafaxine and reduced levels of ODV compared to people with normal CYP2D6 (" extensive metabolizers"). The differences between the CYP2D6 poor and extensive metabolizers, however, are not expected to be clinically important because the sum of venlafaxine and ODV is similar in the two groups and venlafaxine and ODV are pharmacologically approximately equiactive and equipotent
Approximately 87 of a venlafaxine dose is recovered in the urine within 48 hours as unchanged venlafaxine (5 ), unconjugated ODV (29 ), conjugated ODV (26 ), or other minor inactive metabolites (27 ). Renal elimination of venlafaxine and its metabolites is thus the primary route of excretion. Special Populations Age and Gender: Text Continues Below
A population pharmacokinetic analysis of 404 venlafaxine-treated patients from two studies involving both b. i. d. and t. i. d. regimens showed that dose-normalized trough plasma levels of either venlafaxine or ODV were unaltered by age or gender differences. Dosage adjustment based on the age or gender of a patient is generally not necessary (see DOSAGE AND ADMINISTRATION). Extensive/ Poor Metabolizers: Plasma concentrations of venlafaxine were higher in CYP2D6 poor metabolizers than extensive metabolizers. Because the total exposure (AUC) of venlafaxine and ODV was similar in poor and extensive metabolizer groups, however, there is no need for different venlafaxine dosing regimens for these two groups. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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