Paracetamol metabolism was investigated in eight healthy males, eight healthy females and eight healthy females receiving oral contraceptive steroids (OCS). Paracetamol clearance was 22% greater in males compared to the control female group. This difference was entirely due to increased activity of the glucuronidation pathway in males, there being no sex-related differences in the sulphation or oxidative metabolism of paracetamol. Paracetamol clearance in females using OCS was 49% greater than in the control females. Glucuronidation and oxidative metabolism were both induced in OCS users (by 78% and 36% respectively) but sulphation was not altered. Although sex-related differences in paracetamol metabolism are unlikely to be of clinical importance, induction of paracetamol metabolism by OCS may have clinical and toxicological consequences.
PIP: Paracetamol metabolism was investigated in 8 healthy males, 8 healthy females, and 8 healthy females receiving oral contraceptives (OCs). Paracetamol clearance was 22% greater in males compared to the control female group. This difference was entirely due to increased activity of the glucuronidation pathway in males, there being no sex-related differences in the sulphation or oxidative metabolisms of paracetamol. Paracetamol clearance in females using OCs was 49% greater than in the control females. Glucuronidation and oxidative metabolism were both induced in OC users (by 78% and 36% respectively) but sulphation was not altered. Although sex-related differences in paracetamol metabolism are unlikely to be of clinical importance, induction of paracetamol metabolism by OCs may have clinical and toxicological consequences.