NO INTERETHNIC DIFFERENCES IN STEREOSELECTIVE DISPOSITION OF ORAL NIMODIPINE BETWEEN CAUCASIAN AND JAPANESE SUBJECTS

Using stereospecific assays plasma samples of 4 clinical-pharmacologic al studies have been analyzed to obtain enantioselective data on the p harmacokinetics of the calcium channel blocker nimodipine in healthy y oung and elderly Caucasians as well as in healthy young Japanese subje cts. Basic pharmacokinetics (AUC, C-max, t(max), t(1/2)) and dose-prop ortionality based on racemic nimodipine plasma concentrations after or al 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 difference s in AUC and C-max values favoring the (R)-(+)-isomer in respect of hi gher 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 Jap anese subjects. The mean (R)/(S)-ratios for AUC and C-max of all 4 stu dies were quite comparable between the 2 ethnic groups. The available data suggest that there are neither any differences in racemic nimodip ine pharmacokinetics in Caucasians and Japanese subjects nor interethn ic differences in its stereoselective disposition after oral therapeut ic doses.