EFFECTS OF ATORVASTATIN, AN HMG-COA REDUCTASE INHIBITOR, ON HEPATIC OXIDATIVE-METABOLISM OF ANTIPYRINE

Possible effects of multiple-dose administration of atorvastatin on th e pharmacokinetics of single-dose antipyrine were evaluated in this dr ug-drug interaction study. Twelve healthy male volunteers received thr ee 200-mg capsules of antipyrine on days 1 and 22, and two 40-mg atorv astatin tablets in the morning on days 8 through 23, Serial blood and urine samples were collected after administration of each antipyrine d ose. Plasma was analyzed for antipyrine, and urine samples were analyz ed for antipyrine, 4-hydroxyantipyrine, and norantipyrine by validated high-performance liquid chromatography with ultraviolet detection. Ov erall, antipyrine and atorvastatin doses were well tolerated in health y volunteers. Mean antipyrine concentrations in plasma after administr ation of a single, oral dose of antipyrine during coadministration of multiple doses of atorvastatin were nearly superimposible on concentra tions after administration of antipyrine alone. Individual and mean pa rameter values for plasma pharmacokinetics of antipyrine were similar in both treatment periods. Atorvastatin did not significantly alter th e fraction of clearance of antipyrine in plasma that occurred by urina ry excretion of 4-hydroxyantipyrine and norantipyrine. These results i ndicate that the recommended highest daily dose of atorvastatin has ne gligible effects on antipyrine pharmacokinetics and on oxidative pathw ays responsible for the metabolism of antipyrine.