Cilla D D, Gibson D M, Whitfield L R, Sedman A J
Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA.
J Clin Pharmacol. 1996 Jul;36(7):604-9. doi: 10.1002/j.1552-4604.1996.tb04224.x.
The pharmacodynamic 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 15 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.
在16名血脂正常的受试者中，研究了强效的HMG-CoA还原酶抑制剂阿托伐他汀的药效学作用和药代动力学。受试者每日早晨或晚上服用40毫克阿托伐他汀，持续15天。测定血脂和载脂蛋白参数，并根据经过验证的酶抑制生物测定程序测量血浆阿托伐他汀等效浓度。参与者对阿托伐他汀耐受性良好。总体而言，总胆固醇平均降低34%，低密度脂蛋白（LDL）胆固醇降低48%，极低密度脂蛋白（VLDL）胆固醇降低37%，甘油三酯降低25%，载脂蛋白A-I降低6%，载脂蛋白B降低34%。早晨和晚上服用阿托伐他汀后，血脂和载脂蛋白值的变化相似。相比之下，其他HMG-CoA还原酶抑制剂的研究一致表明，晚上给药比早晨给药导致总胆固醇和LDL胆固醇的降低幅度更大。阿托伐他汀等效吸收的速率和程度在晚上给药时低于早晨给药。然而，平均消除半衰期值相似，表明该药物的处置没有昼夜变化。药代动力学差异与对血脂的影响无关。
