Influence of ethnic origin and sex on the pharmacokinetics of clazosentan.
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.
van Giersbergen
Paul L M
PL
Actelion Pharmaceuticals Ltd, Department of Clinical Pharmacology, Gewerbestrasse 16, 4123 Allschwil, Switzerland.
Gunawardena
Kulasiri A
KA
Dingemanse
Jasper
J
D000328:Adult; D044466:Asian People / Q000208:ethnology; D004146:Dioxanes / Q000493:pharmacokinetics*; D065128:Endothelin Receptor Antagonists; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D012737:Sex Factors; D013449:Sulfonamides / Q000493:pharmacokinetics*; D013777:Tetrazoles / Q000493:pharmacokinetics*; D044465:White People / Q000208:ethnology
D004146:Dioxanes; D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D011743:Pyrimidines; D013449:Sulfonamides; D013777:Tetrazoles; C109641:clazosentan