Abstracts

SPM 927 is being developed for the treatment of epilepsy and neuropathic pain. The aim of the present analysis was to characterize possible gender and age differences in the pharmacokinetics (PK) of SPM 927 in healthy elderly subjects ([gt]65 ys.) in comparison to young healthy subjects (18-45 ys.) based on PK data collected in two phase 1 trials: In trial 1, the PK and tolerability of SPM 927 in subjects of different age and gender was evaluated. In trial 2, a potential interaction between SPM 927 and an oral contraceptive was analyzed in female subjects. [underline]Trial 1:[/underline] Analysis of SPM 927 plasma levels was done in 11 elderly males, 12 elderly females and 12 young males. 100 mg SPM 927 od was administered on day 1, 100 mg SPM 927 bid on days 4 to 7, followed by 100 mg od on day 8. [underline]Trial 2:[/underline] Analysis of SPM 927 plasma levels was done in 31 young females. 200 mg SPM 927 was administered bid on days 3-11, followed by 200 mg od on day 12. The PK parameters (AUC and C[sub]max[/sub]) of the two trials were dose-normalized and pooled for analysis. Plasma concentrations of SPM 927 in females were slightly increased compared to males. The AUC ratio of elderly females vs. elderly males was 114% with a 90% confidence interval (CI) of 102-128%. The corresponding C[sub]max[/sub] ratio was 119% with a 90% CI of 107-132%. The AUC ratio of young females vs. young males was 134% with a 90% CI of 122 to 147%. The C[sub]max[/sub] ratio was 142% with a 90% CI of 130 to 154%. Almost all of the differences can be explained by the different body weight. When the parameters are adjusted to body weight, there are no differences between females and males.
Elderly subjects exhibited higher values of C[sub]max[/sub] and AUC than young subjects. The AUC ratio of elderly males vs. young males was 131% with a 90% CI of 117 to 148%. The C[sub]max[/sub] ratio was 129% with a 90% CI of 116 to 143%. The AUC ratio of elderly females vs. young females was 112% with a 90% CI of 102 to 123%. The C[sub]max[/sub] ratio was 108% with a 90% CI of 99 to 117%. The higher values of C[sub]max[/sub] and AUC in elderly subjects can not be explained by differences in body weight. After adjusting of these parameters to body weight, the differences between elderly and young subjects still remain. In summary, there is no effect of gender on the PK of SPM 927 in young and elderly subjects. The higher AUC and C[sub]max[/sub] values in young and elderly females compared to young and elderly males are most likely explained by a lower body weight. As SPM 927 is highly soluble in water, the differences between elderly and young subjects are mainly due to the reduced total body water in elderly subjects which results in higher drug concentrations in this age group. Due to the fact that there is only a slight increase of SPM 927 plasma concentration in elderly and the drug was well tolerated in all groups, the observed differences are considered to be without clinical relevance.