Influence of ethnic origin and sex on the pharmacokinetics of clazosentan

J Clin Pharmacol. 2007 Nov;47(11):1374-80. doi: 10.1177/0091270007307337. Epub 2007 Sep 28.

Abstract

This study investigated the influence of ethnic origin and, as a secondary objective, sex on the pharmacokinetics of the parenteral endothelin receptor antagonist clazosentan in healthy Caucasian and Japanese subjects. Twelve subjects of each ethnic origin (female/male ratio 1:1) were treated with sequential 4-hour infusions of 1, 5, and 15 mg/h. Blood samples were taken frequently to determine plasma levels of clazosentan. The exposure to clazosentan was approximately 16% higher in Japanese subjects compared with Caucasian subjects and 18% higher in females compared with males. These differences were mainly attributable to a difference in clearance. A 3-compartment model well described the plasma concentration-time profiles of clazosentan with disposition half-lives of approximately 6 minutes, 21 minutes, and 2.7 hours. The data suggest that Caucasian and Japanese patients can be treated with a similar dosing regimen of clazosentan. At the doses infused, administration of clazosentan was safe and well tolerated in both ethnic groups.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Asian People* / ethnology
  • Dioxanes / pharmacokinetics*
  • Endothelin Receptor Antagonists
  • Female
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Male
  • Pyridines / pharmacokinetics*
  • Pyrimidines / pharmacokinetics*
  • Sex Factors
  • Sulfonamides / pharmacokinetics*
  • Tetrazoles / pharmacokinetics*
  • White People* / ethnology

Substances

  • Dioxanes
  • Endothelin Receptor Antagonists
  • Pyridines
  • Pyrimidines
  • Sulfonamides
  • Tetrazoles
  • clazosentan