title: Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in Japanese and Caucasian subjects.
abstract: OBJECTIVE
  Aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension. This study compared the pharmacokinetic and pharmacodynamic properties of aliskiren in Japanese and Caucasian subjects.
  
  
  METHODS
  In this open-label, single-centre, parallel-group, single- and multiple-dose study, 19 Japanese and 19 Caucasian healthy young male subjects received a single 300-mg oral dose of aliskiren on day 1 and then aliskiren 300 mg once daily on days 4-10. Blood samples were collected for the measurement of plasma aliskiren concentration, plasma renin concentration (PRC) and plasma renin activity (PRA).
  
  
  RESULTS
  Pharmacokinetic parameters were comparable in Japanese and Caucasian subjects following administration of a single dose of aliskiren {ratio of geometric means: C(max) 1.12 [90% confidence interval (CI) 0.88, 1.43]; AUC(0-72 h) 1.19 [90% CI 1.02, 1.39]} and at steady state [mean ratio: C(max) 1.30 (90% CI 1.00, 1.70); AUC(0-tau) 1.16 (90% CI 0.95, 1.41)]. There was no notable difference in the plasma half-life of aliskiren between Japanese and Caucasian groups (29.7 +/- 10.2 h and 32.0 +/- 6.6 h, respectively). At steady state, peak PRC level and AUC for the concentration-time plot were not significantly different between Japanese and Caucasian subjects (P = 0.64 and P = 0.80, respectively). A single oral dose of aliskiren significantly reduced PRA to a similar extent in Japanese and Caucasian subjects (by 87.5% and 85.7%, respectively, compared with baseline; P < 0.01). Aliskiren was well tolerated by both ethnic groups.
  
  
  CONCLUSIONS
  The oral renin inhibitor aliskiren demonstrated similar pharmacokinetic and pharmacodynamic properties in Japanese and Caucasian subjects.
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. sujata.vaidyanathan@novartis.com
authors.forename: Sujata
authors.initials: S
authors.lastname: Vaidyanathan
authors.forename: Joanne
authors.initials: J
authors.lastname: Jermany
authors.forename: Chingming
authors.initials: C
authors.lastname: Yeh
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Bizot
authors.forename: Riccardo
authors.initials: R
authors.lastname: Camisasca
mesh_terms: D000328:Adult; D000577:Amides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects; D005650:Fumarates / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D044465:White People / Q000235:genetics*; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren