Pan H Y, Waclawski A P, Funke P T, Whigan D
Du Pont Merck Pharmaceutical Company, Wilmington, DE 19880.
Ann Pharmacother. 1993 Sep;27(9):1029-33. doi: 10.1177/106002809302700902.
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.
Open, single-dose study.
Clinical Pharmacology Unit of Princeton Medical Center for study in men and Hill Top Pharmatest, Cincinnati, for study in women.
Normal, healthy male (aged 19-75 y) and female (aged 18-78 y) volunteers.
Subjects received a single 20-mg dose of pravastatin after an overnight fast.
The maximum plasma pravastatin concentration (Cmax), time required for that concentration to develop (Tmax), and the elimination half-life (beta t1/2). Serum concentrations of pravastatin and its major metabolite, the 3-alpha 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.
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, Cmax and beta t1/2 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.
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.
评估年龄对普伐他汀在男性和女性体内药代动力学的影响。次要目的是评估口服避孕药类固醇对年轻女性体内普伐他汀药代动力学的影响。
开放、单剂量研究。
普林斯顿医学中心临床药理学组用于男性研究，辛辛那提的山顶药物测试中心用于女性研究。
正常、健康的男性（19 - 75岁）和女性（18 - 78岁）志愿者。
受试者在空腹过夜后接受单次20毫克普伐他汀剂量。
普伐他汀的最大血浆浓度（Cmax）、达到该浓度所需的时间（Tmax）以及消除半衰期（β t1/2）。在给药后0.33至48小时的12个时间点测定普伐他汀及其主要代谢产物3-α异构体SQ 31,906的血清浓度。在同一时期累积收集尿液，以测定普伐他汀和SQ 31,906的尿排泄量。这两项指标均用于确定药代动力学参数。
普伐他汀和SQ 31,906在年轻和老年男性及女性受试者中的药代动力学特征差异不大。尽管老年受试者中普伐他汀浓度时间曲线下的平均面积较高，老年女性中显著更高，但年轻和老年志愿者的Cmax和β t1/2值相似。年轻女性同时服用口服避孕药不影响普伐他汀或SQ 31,906的药代动力学。
普伐他汀的药代动力学在老年男性或女性中无需调整剂量。在男性和女性中，母体药物或其代谢产物的处置未检测到差异。
