Pharmacokinetics of Pravastatin in Elderly versus Young Men and Women

Abstract

OBJECTIVE:

To assess the effect of age on the pharmacokinetics of pravastatin in men and women. A secondary objective was to evaluate the effect of oral contraceptive steroids on the pharmacokinetics of pravastatin in young women.

DESIGN:

Open, single-dose study.

SETTING:

Clinical Pharmacology Unit of Princeton Medical Center for study in men and Hill Top Pharmatest, Cincinnati, for study in women.

PARTICIPANTS:

Normal, healthy male (aged 19–75 y) and female (aged 18–78 y) volunteers.

INTERVENTIONS:

Subjects received a single 20-mg dose of pravastatin after an overnight fast

MAIN OUTCOME MEASURES:

The maximum plasma pravastatin concentration (C_max), time required for that concentration to develop (T_max). and the elimination half-life (βt1/2). Serum concentrations of pravastatin and its major metabolite, the 3-α isomer, SQ 31,906, were determined at 12 intervals from 0.33 to 48 hours after the dose. Urine was collected cumulatively during the same period to determine urinary excretion of pravastatin and SQ 31,906. Both measures were used to determine pharmacokinetic parameters.

RESULTS:

The pharmacokinetic profiles of pravastatin and SQ 31,906 in young and elderly subjects of men and women differed little. Although the mean area under the concentration time curve of pravastatin was higher in the elderly and significantly higher in the elderly women, C_max and βt1/2 values were similar in the young and the elderly volunteers. Concomitant administration of oral contraceptives in young women did not affect 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 disposition of the parent drug or its metabolite in men and women.