QUINIDINE DOES NOT ALTER ANTIPYRINE METABOLISM

Quinidine has been reported to be a potent inhibitor of a specific isozyme of cytochrome P‐450 (P‐450db 1) that is responsible for the metabolism of a select group of drugs. In order to investigate the potential for quinidine to inhibit other isozymes of cytochrome P‐450 and to assess whether or not P‐450db 1 plays any role in antipyrine metabolism, we studied the effects of quinidine pretreatment on the pharmacokinetics and metabolism of antipyrine in six healthy, male volunteers. Using a randomized, crossover study design with a 2‐week washout period between treatments, subjects received a single 1 gram antipyrine dose alone or with quinidine sulfate 200 mg orally every 8 hours for 24 hours prior to the dose of antipyrine and over the 48 hours following antipyrine administration. Mean serum concentrations, apparent oral clearance (1.93 ± 0.86 vs 2.06 ± 1.06 L/hr with quinidine) and half‐life (13.5 ± 3.3 vs 12.4 ± 3.6 hr with quinidine) were not significantly different between the two treatments. The fraction of the administered dose recovered as antipyrine and measured metabolites (56.7% vs 59% with quinidine) as well as the recovery of each individual metabolite was not altered with quinidine pretreatment. In addition, the mean formation clearances for norantipyrine, 4‐hydroxyantipyrine and 3‐hydroxymethylantipyrine exhibited no change between treatment phases. These results suggest that the effects of quinidine on the cytochrome P‐450 system are highly specific for particular isozymes, that the isozymes involved in metabolism of antipyrine to its major metabolites are not affected and that P‐450db 1 is not involved in the formation of any of the major metabolites of antipyrine. 1990 American College of Clinical Pharmacology