¹Novartis Pharma AG, Novartis Pharmaceuticals Corporation, Basel, Switzerland

Abstract

Background: Combination of the oral renin inhibitor aliskiren with a diuretic is expected to provide increased antihypertensive efficacy. This study investigated the pharmacokinetics of aliskiren, alone or in combination with the diuretic hydrochlorothiazide (HCTZ).

Methods: Open-label, two-period, multiple dose study in 22 healthy volunteers aged 18-45 years. Subjects received HCTZ 25 mg once daily on days 1-4 followed by a 4-day wash out. Aliskiren 300 mg once daily was administered on days 9-19 with HCTZ 25 mg added on days 16-19. Blood samples were taken on days 4, 15 and 19 for pharmacokinetic profiling.

Results: Steady-state AUC_0- values for aliskiren (meanSD) were not significantly altered by HCTZ (aliskiren AUC_0- 2310934 alone vs 22101157 ng.h/mL with HCTZ, ratio of geometric means 0.93[90% CI 0.83-1.05]). Aliskiren C_maxwas slightly lowered by HCTZ (aliskiren C_max 425216 vs 309150 ng/mL, mean ratio 0.78[0.64-0.95]) but this is unlikely to be of clinical significance. Median t_max values for aliskiren were essentially unchanged (aliskiren t_max 2.2 vs 1.5h). Steady-state AUC_0-and C_max for HCTZ were slightly decreased by aliskiren (mean ratios: AUC_0- 0.90[0.87-0.93]; C_max 0.74[0.69-0.79]) but these changes are unlikely to be clinically significant. Aliskiren was well tolerated in combination with HCTZ.

Conclusions: In healthy volunteers, aliskiren was well tolerated in combination with HCTZ and drug interactions were either insignificant or of unlikely clinical significance.