title: Single-dose pharmacokinetics of the renin inhibitor ACT-077825 in elderly and young subjects of both sexes.
abstract: OBJECTIVE
  The study objective was to investigate and compare the pharmacokinetics of a single oral dose of ACT-077825, a novel direct renin inhibitor, in young and elderly, male and female healthy subjects and to evaluate the safety and tolerability of ACT-077825 in these population groups.
  
  
  METHODS
  A total of 32 healthy subjects were included in this single-center, open-label study. The subjects were divided into 4 groups, including 8 young male, 8 young female, 8 elderly male and 8 elderly female subjects. Each participant received a single 200-mg dose of ACT-077825. Blood samples were taken over 5 days (120 h) to determine the plasma levels of ACT-077825. Safety and tolerability were monitored using standard assessments before drug administration, on the administration day and at the end of the blood sampling period.
  
  
  RESULTS
  Upon pooling male and female subjects, exposure was higher in elderly compared to young subjects, showing an increase of 65% for AUC0-∞, 40% for Cmax and 38% for t1/2. While young male and female subjects showed similar plasma profiles and exposure, a significant increase in exposure occurred with age in both sexes compared to younger subjects. The difference was largest between young and elderly females. Furthermore, the exposure to ACT-077825 was around 30% higher in elderly female compared to elderly male subjects. ACT-077825 was well tolerated by all groups, including the elderly females who showed the highest exposure.
  
  
  CONCLUSIONS
  ACT-077825 exposure is moderately increased in elderly subjects. The clinical relevance of this observation should be explored in the context of further studies.
authors.affiliation: Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
authors.forename: Marzia
authors.initials: M
authors.lastname: Cavallaro
authors.forename: Urte
authors.initials: U
authors.lastname: Eydeler
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D012737:Sex Factors; D014050:Toluene / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000092502:Renin Inhibitors
chemical_list: D000959:Antihypertensive Agents; D014050:Toluene; D000092502:Renin Inhibitors; C554657:MK-8141