Effect of single and multiple doses of sulphinpyrazone on antipyrine metabolism and urinary excretion of 6-beta-hydroxycortisol.

Sulphinpyrazone decreases the plasma clearance of tolbutamide and S-warfarin and increases the clearance of R-warfarin, theophylline and antipyrine. In order to determine whether sulphinpyrazone is an inducer or inhibitor or both of oxidative drug metabolism, antipyrine and its metabolites as well as 6-beta-hydroxycortisol were measured in urine before, 24 h and after 23 days of chronic administration of sulphinpyrazone (4 X 200 mg/day). During chronic treatment sulphinpyrazone increased the ratio of 6-beta-hydroxycortisol to the 17-hydroxycorticosteroids by 70% (p less than 0.02). The renal clearance of the main oxidative metabolites of antipyrine (4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine) were increased after sulphinpyrazone (p less than 0.02). Except for norantipyrine, no change in total excretion of antipyrine and its metabolites occurred after 24 h or after 23 days. It is concluded that sulphinpyrazone induces the enzymes which metabolize antipyrine and cortisol.