Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in Japanese and Caucasian subjects

Aliskiren is the first in a new class of orally effective renin inhibitors. This study compared the single and multiple dose pharmacokinetics and pharmacodynamics of aliskiren in healthy male Japanese (J) and Caucasian (C) subjects. The study was an open label, single center, parallel group single and multiple dose study. A total of 38 healthy male subjects (19 J, 19 C) aged 20–45 years each received a single 300 mg oral dose of aliskiren on day 1, followed by aliskiren 300 mg once daily on days 4–10. Plasma samples were taken at regular intervals throughout the dosing period for determination of aliskiren concentrations and plasma renin activity (PRA). Data are presented as the mean ± standard deviation. Following administration of a single 300 mg oral dose, exposure to aliskiren was slightly, but not significantly higher in Japanese subjects (Cmax: J 215±122 vs C 186±91 ng/mL; AUC0–72h: J 1387±615 vs C 1124±339 ng.h/mL). Similar results were obtained at steady state following multiple doses of aliskiren (Cmax: J 403±193 vs C 321±189 ng/mL; AUC0–τ: J 2519±1179 vs C 2135±791 ng.h/mL). t½ values were comparable for the two groups (t½: J 29.7±10.2 vs C 32.0±6.6 h). Comparison of Cmax values following single and multiple doses indicated an accumulation factor of approximately 2 for both Japanese and Caucasian subjects. PRA was numerically higher in Japanese subjects at baseline (J 0.24±0.21 vs C 0.14±0.14 ng/mL/h), but a single 300 mg dose of aliskiren significantly (P<0.01) inhibited PRA to a similar level in both groups (PRA at 2 hours post-dose: J 0.03±0.02 vs C 0.02±0.01 ng/mL/h). On-treatment PRA values at steady state following multiple doses of aliskiren showed no significant differences between groups. Aliskiren treatment was well tolerated by both Japanese and Caucasian subjects. A total of 46 adverse events (AEs) were reported in 21 subjects, and the distribution of AEs between the two groups was approximately equal. All reported AEs were mild to moderate in severity, except for one report of dizziness in a Caucasian subject that was judged not to be related to the study drug. In conclusion, single and multiple doses of aliskiren 300 mg were well tolerated and exhibited comparable pharmacokinetic and pharmacodynamic properties in healthy male Japanese and Caucasian subjects.