Influence of Severe Renal Impairment on the Pharmacokinetics of Clazosentan

被引:7
|
作者
Bruderer, Shirin [1 ]
Sasu, Boris [2 ]
Tsvitbaum, Nahum [2 ]
Dingemanse, Jasper [1 ]
机构
[1] Actelion Pharmaceut Ltd, Clin Pharmacol, CH-4123 Allschwil, Switzerland
[2] INNOPHAR Innovat Pharma Res, State Med Sanit Inst, Kishinev, Moldova
来源
JOURNAL OF CLINICAL PHARMACOLOGY | 2011年 / 51卷 / 03期
关键词
Clazosentan; endothelin; renal impairment; pharmacokinetics; ENDOTHELIN RECEPTOR ANTAGONIST; ANEURYSMAL SUBARACHNOID HEMORRHAGE; CEREBRAL VASOSPASM; CYCLOSPORINE-A; PREVENTION; TOLERABILITY; BOSENTAN;
D O I
10.1177/0091270010368975
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The purpose of this open-label, parallel-group study was to investigate the effect of severe renal impairment on the pharmacokinetics (PK), tolerability, and safety of clazosentan, an intravenous endothelin receptor antagonist. Clazosentan was administered as a continuous intravenous infusion of 1 mg/h for a period of 6 hours in 9 subjects with severe renal impairment (group A) and 8 healthy subjects (group B) (creatinine clearance <30 mL/min and >80 mL/min, respectively). The subjects in both groups were well matched for sex, body mass index, and age (+/- 10 years). The PK parameters of clazosentan were calculated by both model-independent and model-dependent methods. The differences in the PK parameters between the subjects with severe renal impairment and healthy subjects were minor. The geometric means for area under the curve (AUC) during the infusion, AUC(0-t') (AUC from zero to time t of the last measured concentration above the limit of quantification) AUC(0-infinity) (AUC from zero to infinity), and concentration at steady state were 7%, 8%, 8%, and 8%, respectively, higher in group A than in group B. The results obtained after 2-compartmental modeling were in agreement with those obtained after noncompartmental analysis. Administration of clazosentan was well tolerated in both groups. The data suggest that there is no need for dose adjustment of clazosentan in patients with renal impairment.
引用
收藏
页码:413 / 421
页数:9
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