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

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 randomi zed as age-matched? male-female pairs and stratified into younger (18-65 ye ars, premenopausal females) or older (65-85 years, postmenopausal females) groups. Thirty-two (16 female, 16 male) subjects received 0.2 mg cerivastat in daily for 7 days; 17 received placebo. Between all males and females, no differences in cerivastatin pharmacokinetics were observed. The AUC(norm) in older females was 21% higher than in older males, while the AUC(norm) in younger females was 26% lower than in younger males. The C-max in older fe males was 30% higher than in age-matched males or younger males and females , All other pharmacokinetic parameters, including half-life, t(max), accumu lation 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-emerg ent elevations (< 2xULN) in creatine kinase occurred in one subject. Transa minase elevations occurred in nine subjects, most were less than 3xULN, and were equally distributed between groups. In conclusion, cerivastatin was w ell tolerated. The minor differences in the pharmacokinetics of cerivastati n 0.2 mg between genders does not require modification of dosage.