OBJECTIVE: The purpose of this study was to investigate the effect of gender on the tolerability, safety and pharmacokinetics of clazosentan, an intravenous endothelin receptor antagonist. METHODS: Clazosentan was infused at a dosage of 0.05 mg/kg/h or 0.1 mg/kg/h for 72 hours in 8 female and 8 male healthy volunteers, respectively. Tolerability and safety were assessed via the recording of dose reductions/infusion stops, vital signs, ECG, adverse events and clinical laboratory variables. Blood samples were collected for the determination of clazosentan and endothelin-1 concentrations. RESULTS: The occurrence of adverse events such as headache, vomiting and nausea of moderate to severe intensity led either to discontinuation of the infusion or to a dose reduction in the majority of volunteers. The values (mean and 95% confidence intervals) for clearance were 37.7 (32.8, 43.4) and 35.2 (27.8, 44.5) L/h in male and female volunteers, respectively. CONCLUSION: Long-term infusion of clazosentan at the doses tested was poorly tolerated in both male and female volunteers. Gender appeared to have no influence on the pharmacokinetics of clazosentan.
OBJECTIVE: The purpose of this study was to investigate the effect of gender on the tolerability, safety and pharmacokinetics of clazosentan, an intravenous endothelin receptor antagonist. METHODS:Clazosentan was infused at a dosage of 0.05 mg/kg/h or 0.1 mg/kg/h for 72 hours in 8 female and 8 male healthy volunteers, respectively. Tolerability and safety were assessed via the recording of dose reductions/infusion stops, vital signs, ECG, adverse events and clinical laboratory variables. Blood samples were collected for the determination of clazosentan and endothelin-1 concentrations. RESULTS: The occurrence of adverse events such as headache, vomiting and nausea of moderate to severe intensity led either to discontinuation of the infusion or to a dose reduction in the majority of volunteers. The values (mean and 95% confidence intervals) for clearance were 37.7 (32.8, 43.4) and 35.2 (27.8, 44.5) L/h in male and female volunteers, respectively. CONCLUSION: Long-term infusion of clazosentan at the doses tested was poorly tolerated in both male and female volunteers. Gender appeared to have no influence on the pharmacokinetics of clazosentan.
Authors: M Yanagisawa; H Kurihara; S Kimura; Y Tomobe; M Kobayashi; Y Mitsui; Y Yazaki; K Goto; T Masaki Journal: Nature Date: 1988-03-31 Impact factor: 49.962
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Authors: A Giaid; M Yanagisawa; D Langleben; R P Michel; R Levy; H Shennib; S Kimura; T Masaki; W P Duguid; D J Stewart Journal: N Engl J Med Date: 1993-06-17 Impact factor: 91.245