Influence of sex and oral contraceptive steroids on paracetamol metabolism.

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.