Influence of phenylbutazone, mofebutazone and aspirin on the pharmacokinetics of dexamethasone in the rat.

Phenylbutazone suppresses the C-6 hydroxylation, absorption rate, bioavailability, and renal and plasma clearanceè rates of dexamethasone administered orally to normal and oedemateous rats. It increases the half life and the volume of distribution. Aspirin exerts an effect which is less pronounced and involves the enhancement of the C-6 hydroxylation. Aspirin suppresses the half life and renal clearance of dexamethasone and enhances its hepatic clearance. Mofebutazone does not exert any pronounced influence. Also, unlike phenylbutazone, it does not interfere with the gastrointestinal absorption of dexamethasone. More rapid onset of absorption, decrease of half life and increase of the contribution of renal clearance to total plasma clearance of dexamethasone, are characteristics of the oedematous condition in the rat. The contribution of renal clearance to the elimination of dexamethasone is much greater in the rat than in human subjects. The presence of a third unconjugated metabolite of dexamethaone in the urine of rat has been demonstrated.