Pharmacodynamics, safety, tolerability, and pharmacokinetics of the 0.8-mg dose of cerivastatin in patients with primary hypercholesterolemia

被引:36
作者
Stein, E
Isaacsohn, J
Stoltz, R
Mazzu, A
Liu, MC
Lane, C
Heller, AH
机构
[1] Metab & Atherosclerosis Res Ctr, Cincinnati, OH 45219 USA
[2] GFI Pharmaceut Serv Inc, Evansville, IN USA
[3] Bayer Corp, Div Pharmaceut, West Haven, CT USA
关键词
D O I
10.1016/S0002-9149(99)00120-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cerivastatin is a third generation hydroxy-methyl-glutaryl-Co-enzyme A (HMG-CoA) reductase inhibitor proven to lower low-density lipoprotein (LDL) cholesterol 28% to 31% in patients with primary hypercholesterolemia when given at 0.3 mg/day. This study evaluates the safety, tolerability, pharmacodynamics, and pharmocokinetics of cerivastatin 0.8 mg once daily for 4 weeks. In this randomized, double-blind, placebo-controlled parallel group trial conducted at 2 study centers, 41 patients (63% women) with primary hypercholesterolemia were placed on an American Heart Association Step 1 diet for 4 weeks. Single-blind placebo was administered for the final 2 weeks, before randomization. Patients received cerivastatin 0.8 mg (n = 28) or placebo (n = 13) once each evening for 28 days. Cerivastatin at 0.8 mg daily was well tolerated. No discontinuations occurred during the study. Adverse events were mild and transient. One cerivastatin-treated patient experienced asymptomatic creatinine kinase, 8 x the upper limit of normal (ULN) elevation on the last day of the study, which resolved 6 days after the completion of the study. Cerivastatin 0.8 mg daily significantly reduced LDL cholesterol compared with placebo (-44.0 +/- 2.0% vs 2.2 +/- 2.8%, p <0.0001); total cholesterol (-30.8 +/- 1.4% vs 2.6 +/- 2,1%, p <0.0001), triglycerides (-11.2 +/- 5.9% vs 15.9 +/- 8.6%, p < 0.02), but did not significantly alter high-density lipoprotein (HDL) cholesterol (3.2 +/- 2.1% vs -1.2 +/- 3,1%, p = NS). The pharmacokinetics of the 0.8-mg dose revealed dose proportional elevations in the 24-hour area under the curve and maximum plasma concentration relative to 0.3- and 0.4-mg doses with no change in time to maximum concentration or the elimination half-life in plasma. The increased efficacy and lack of clinically significant laboratory abnormalities or adverse events demonstrates a need for a large long-term study to confirm the safety and efficacy of this dose of cerivastatin. (C) 1999 by Excerpta Medica, Inc.
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页码:1433 / 1436
页数:4
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