| Literature DB >> 2312782 |
S K Bowles1, L Cardozo, D J Edwards.
Abstract
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.(ABSTRACT TRUNCATED AT 250 WORDS)Entities:
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Year: 1990 PMID: 2312782 DOI: 10.1002/j.1552-4604.1990.tb03471.x
Source DB: PubMed Journal: J Clin Pharmacol ISSN: 0091-2700 Impact factor: 3.126