PHARMACOKINETICS OF PRAVASTATIN IN ELDERLY VERSUS YOUNG MEN AND WOMEN

OBJECTIVE: To assess the effect of age on the pharmacokinetics of prav astatin in men and women. A secondary objective was to evaluate the ef fect of oral contraceptive steroids on the pharmacokinetics of pravast atin in young women. DESIGN: Open, single-dose study. SETTING: Clinica l Pharmacology Unit of Princeton Medical Center for study in men and H ill Top Pharmatest, Cincinnati, for study in women. PARTICIPANTS: Norm al, healthy male (aged 19-75 y) and female (aged 18-78 y) volunteers. INTERVENTIONS: Subjects received a single 20-mg dose of pravastatin af ter an overnight fast. MAIN OUTCOME MEASURES: The maximum plasma prava statin concentration (C(max)), time required for that concentration to develop (T(max)), and the elimination half-life (betat1/2). Serum con centrations of pravastatin and its major metabolite, the 3-alpha isome r, SQ 31,906, were determined at 12 intervals from 0.33 to 48 hours af ter the dose. Urine was collected cumulatively during the same period to determine urinary excretion of pravastatin and SQ 31,906. Both meas ures were used to determine pharmacokinetic parameters. RESULTS: The p harmacokinetic profiles of pravastatin and SQ 31,906 in young and elde rly subjects of men and women differed little. Although the mean area under the concentration time curve of pravastatin was higher in the el derly and significantly higher in the elderly women, C(max) and betat1 /2 Values were similar in the young and the elderly volunteers. Concom itant administration of oral contraceptives in young women did not aff ect the pharmacokinetics of pravastatin or SQ 31,906. CONCLUSIONS: The pharmacokinetics of pravastatin do not necessitate dosage adjustments in elderly men or women. No differences were detected between the dis position of the parent drug or its metabolite in men and women.