Influence of gender on the pharmacokinetics, safety, and tolerability of cerivastatin in healthy adults

• Published in: European journal of clinical pharmacology Vol. 56; no. 12; pp. 897 - 903
• Main Authors: ISAACSOHN, J, ZINNY, M, MAZZU, A, LETTIERI, J, HELLER, A. H
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-03-2001; Berlin Springer Nature B.V
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Area Under Curve; Biological and medical sciences; Chromatography, High Pressure Liquid; Double-Blind Method; Drug therapy; Drug Tolerance; Female; Females; General and cellular metabolism. Vitamins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Male; Males; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pyridines - adverse effects; Pyridines - blood; Pyridines - pharmacokinetics; Sex Factors; Statins; Human; Healthy subject; Enzyme; Toxicity; Sex; Oral administration; Enzyme inhibitor; Male; Statin derivative; Cerivastatin; Multiple dose; Female; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Pharmacokinetics; Age; Antilipemic agent
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s002280000225

The pharmacokinetics, safety, and tolerability of cerivastatin, a synthetic HMG-CoA reductase inhibitor were studied in 49 healthy volunteers. In this double-blind, parallel group, multiple-dose study, volunteers were randomized as age-matched, male-female pairs and stratified into younger (18-65 years, premenopausal females) or older (65-85 years, postmenopausal females) groups. Thirty-two (16 female, 16 male) subjects received 0.2 mg cerivastatin daily for 7 days; 17 received placebo. Between all males and females, no differences in cerivastatin pharmacokinetics were observed. The AUCnorm in older females was 21% higher than in older males, while the AUCnorm in younger females was 26% lower than in younger males. The Cmax in older females was 30% higher than in age-matched males or younger males and females. All other pharmacokinetic parameters, including half-life, tmax, accumulation ratios, and steady state plasma levels were similar in all treatment groups. The most common adverse events, including headache (4), dyspepsia (4), and rash (4), were equally distributed between groups. Treatment-emergent elevations (< 2 x ULN) in creatine kinase occurred in one subject. Transaminase elevations occurred in nine subjects, most were less than 3 x ULN, and were equally distributed between groups. In conclusion, cerivastatin was well tolerated. The minor differences in the pharmacokinetics of cerivastatin 0.2 mg between genders does not require modification of dosage.