Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening
Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening
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DOI：
10.1002/j.1552-4604.1996.tb04224.x
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发表时间：
1996-07-01
影响因子：
2.9
通讯作者：
Sedman, AJ
中科院分区：
文献类型：
--
作者：
Cilla, DD;Gibson, DM;Sedman, AJ
本文研究了HMG-CoA还原酶抑制剂阿托伐他汀对16例正常血脂受试者的药效学和药代动力学。测定血脂和载脂蛋白参数，并根据有效的酶抑制生物测定程序测定阿托伐他汀的血浆当量浓度。受试者对阿托伐他汀的耐受性良好。总体而言，观察到总胆固醇、低密度脂蛋白胆固醇、极低密度脂蛋白胆固醇、甘油三酯、载脂蛋白A-I和载脂蛋白B的平均降幅分别为34%、48%、37%、25%、6%和34%。早晨和晚上服用阿托伐他汀后，血脂和载脂蛋白的变化相似。相比之下，对其他HMG-CoA还原酶抑制剂的研究一直表明，晚上服用比早上服用更能降低总胆固醇和低密度脂蛋白。晚间给药阿托伐他汀的等量吸收速率和吸收程度均低于早间给药。然而，平均消除半衰期值是相似的，这表明这种药物的处置没有日间变化。药代动力学差异与对血脂的影响无关。
The phormacodynamic effects and pharmacokinetics of atorvastatin, a potent investigational inhibitor of HMG-CoA reductase, were studied in 16 normolipidemic subjects after administration of 40 mg daily for 25 days in the morning or evening. Lipid and apolipoprotein parameters were determined, and plasma atorvastatin equivalent concentrations were measured according to a validated enzyme inhibition bioassay procedure. Atorvastatin was well tolerated by the participants. Overall, mean reductions of 34% in total cholesterol, 48% in low-density lipoprotein (LDL) cholesterol, 37% in very low density lipoprotein (VLDL) cholesterol, 25% in triglycerides, 6% in apolipoprotein A-I, and 34% in apolipoprotein B were observed. Changes in lipid and apolipoprotein values were similar after morning and evening administration of atorvastatin. In contrast, studies with other HMG-CoA reductase inhibitors have consistently shown that evening administration results in larger reductions in total and LDL cholesterol than does morning administration. Rate and extent of equivalent absorption of atorvastatin were lower during evening than morning administration. Mean elimination half-life values were similar, however, suggesting that there is no diurnal variation in disposition of this drug. Pharmacokinetic differences did not correlate with effects on serum lipids.