No interethnic differences in stereoselective disposition of oral nimodipine between Caucasian and Japanese subjects.
Using stereospecific assays plasma samples of 4 clinical-pharmacological studies have been analyzed to obtain enantioselective data on the pharmacokinetics of the calcium channel blocker nimodipine in healthy young and elderly Caucasians as well as in healthy young Japanese subjects. Basic pharmacokinetics (AUC, C(max), t(max), t1/2) and dose-proportionality based on racemic nimodipine plasma concentrations after oral single doses of 30, 60, and 90 mg were comparable in Caucasian and Japanese subjects. Stereoselective disposition of nimodipine could be observed in all cases investigated, resulting in pronounced differences in AUC and C(max) values favoring the (R)-(+)-isomer in respect of higher oral bioavailability: After single doses of 60 mg nimodipine, for instance, (R)/(S)-ratios for AUC were ranging from 5.5 - 10.0 (g.mean/SD: 7.4/1.3) in young Caucasians, for C(max) from 4.4 - 7.7 (g.mean/SD: 5.9/1.3). Corresponding ranges of 4.7 - 5.5 (g.mean/SD: 5.0/1.1) and 4.5 - 6.5 (g.mean/SD: 5.0/1.2), respectively, were calculated for Japanese subjects. The mean (R)/(S)-ratios for AUC and C(max) of all 4 studies were quite comparable between the 2 ethnic groups. The available data suggest that there are neither any differences in racemic nimodipine pharmacokinetics in Caucasians and Japanese subjects nor interethnic differences in its stereoselective disposition after oral therapeutic doses.
Mück
W
W
Institute of Clinical Pharmacology, Pharma Research Center, Bayer AG, Wuppertal, Germany.
Tanaka
T
T
Ahr
G
G
Kuhlmann
J
J
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000097:blood / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D044465:White People
D002121:Calcium Channel Blockers; D009553:Nimodipine