title: An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin.
abstract: OBJECTIVE
  To assess the effect of age and gender on the pharmacokinetics (PK) of the ghrelin receptor agonist anamorelin.
  
  
  METHODS
  Three demographic cohorts of healthy subjects were enrolled in this single-center, open-label study. Subjects received a single oral dose (25 mg) of anamorelin HCl. Serial blood samples were collected over 24 hours to assess anamorelin PK and circulating growth hormone (GH) levels. Data were compared with a reference cohort.
  
  
  RESULTS
  Anamorelin was rapidly absorbed in all cohorts; peak concentrations were observed 30-45 minutes and 2-4 hours post-dose, which declined biexponentially with mean terminal half-lives of 6-7 hours. An age effect on Cmaxand AUC∞was not apparent; however, mean AUC∞values were approximately 1.8-1.9-fold higher in the female cohorts than in the reference male cohort. GH increase was rapid and virtually identical in both sexes, though attenuated in elderly subjects. No clinically significant safety or tolerability findings were observed.
  
  
  CONCLUSIONS
  While PK parameters do suggest higher exposure in females, this effect is considered to be modest given the variability of the 6-8 subjects per cohort. Moreover, no such effect was observed in the pharmacodynamic responses, thus, dose adjustment for age and gender is considered unnecessary.
authors.affiliation: Quintiles Phase I Services, Inc. Overland Park, KS, USA.
authors.forename: Philip T
authors.initials: PT
authors.lastname: Leese
authors.affiliation: PK/PD International, Inc. Tucson, AZ, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Trang
authors.affiliation: Buffalo Clinical Research Center LLC Buffalo, NY, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Blum
authors.affiliation: Helsinn Therapeutics (US), Inc. Bridgewater, NJ, USA.
authors.forename: Eleanor
authors.initials: E
authors.lastname: de Groot
keywords: age; anamorelin; cancer cachexia; gender; pharmacokinetics