Tolerability, pharmacokinetics, and pharmacodynamics of clazosentan, a parenteral endothelin receptor antagonist.

European Journal of Clinical Pharmacology
Paul L M van Giersbergen, Jasper Dingemanse

Abstract

The purpose of this study was to investigate in healthy male subjects the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of clazosentan, an intravenous endothelin receptor antagonist. Clazosentan was infused at doses of 3-60 mg/h for 3 h, 60 mg/h for 6 h and at 30 mg/h for 12 h. Each dose was given to a separate group of subjects, six of whom received clazosentan and two placebo. Vital signs, ECG, adverse events, and clinical laboratory variables were monitored to assess tolerability. Blood and urine samples were collected frequently for pharmacokinetic and pharmacodynamic determinations. Infusion of clazosentan up to doses of 30 mg/h for 3 h was well tolerated. A dose of 60 mg/h and longer infusions were less well tolerated and three subjects did not complete the 12-h infusion of 30 mg/h due to adverse events. Headache was the most commonly reported adverse event followed by nausea, vomiting, and nasal congestion. The pharmacokinetics of clazosentan were dose proportional in the dose range investigated. Values (mean and 95% confidence intervals) for clearance and volume of distribution at a dose of 10 mg/h for 3 h were 42.2 (36.6, 48.7) l/h and 32.4 (27.0, 38.8) l, respectively. Both variables were ind...Continue Reading

References

Oct 1, 1982·Journal of Pharmacokinetics and Biopharmaceutics·K K Chan, M Gibaldi
Mar 30, 1994·Biochemical and Biophysical Research Communications·T FukurodaM Nishikibe
Feb 1, 1997·Acta Physiologica Scandinavica·J PernowL Kaijser
Mar 20, 1999·The Journal of Nutrition·M J HamadehL J Hoffer
Oct 6, 2000·Drug Discovery Today·A RayJ B Gupta
May 22, 2002·Journal of Cardiovascular Pharmacology·Jasper DingemansePaul L M van Giersbergen
Jul 24, 2002·European Journal of Clinical Pharmacology·Paul L M van GiersbergenJasper Dingemanse
Jan 20, 2004·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·L E SpiekerT F Lüscher
Mar 18, 2006·British Journal of Clinical Pharmacology·Jasper DingemansePaul L M van Giersbergen
Jan 1, 1994·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·N W Dorsch, M T King

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Citations

May 5, 2011·European Journal of Clinical Pharmacology·Patricia N SidhartaJasper Dingemanse
Oct 17, 2008·Expert Opinion on Investigational Drugs·R Loch Macdonald
Oct 2, 2007·Journal of Clinical Pharmacology·Paul L M van GiersbergenJasper Dingemanse
Dec 15, 2010·British Journal of Clinical Pharmacology·Shirin BrudererJasper Dingemanse
Oct 12, 2010·Journal of Clinical Pharmacology·Shirin BrudererJasper Dingemanse
Jun 9, 2016·Journal of Medicinal Chemistry·John-David Aubert, Lucienne Juillerat-Jeanneret
Feb 14, 2018·Stroke; a Journal of Cerebral Circulation·Hanhan LiuNicole A Terpolilli
Dec 12, 2019·Pharmaceutical Research·Anke-Katrin VolzThorsten Lehr
Mar 22, 2020·Journal of Clinical Medicine·Frederik C EnevoldsenMarcus Krüger
Jan 4, 2021·Journal of Pharmacokinetics and Pharmacodynamics·Andrea HenrichAndreas Krause

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