Gender and oral contraceptive steroids as determinants of drug glucuronidation: effects on clofibric acid elimination

Abstract

The disposition of clofibric acid, a drug metabolised largely by glucuronidation, was studied in eight males, eight females and eight females receiving oral contraceptive steroids (OCS). Clofibric acid plasma clearance was not significantly different in males compared to the control female group but was 48% greater (P less than 0.01) in women receiving OCS compared to non-pill using females. This difference was due to an alteration in clofibric acid metabolic clearance as there were no differences between the groups in clofibric acid free fraction. Along with previous data the results suggest that induction of drug glucuronidation by OCS may be of clinical importance, although any sex-related differences are unlikely to be of clinical significance.

PIP: The disposition of clofibric acid, a drrug metabolized largely by glucuronidation, was studied in 8 males, 8 females, and 8 females receiving oral contraceptives (OCs). Clofibric acid plasma clearance was not significantly different in males compared with the control female group but was 48% greater (P less than 0.01) in women receiving OCs compared with nonpill-using females. This difference was due to an alteration in clofibric acid metabolic clearance because there were no differences between the groups in clofibric acid free fraction. Along with previous data, the results suggest that induction of drug glucuronidation by OCs may be of clinical importance, although any sex-related differences are unlikely to be of clinical significance.