Article (Author postprint) (213 Kb) - Limited access to UNIGE
Other version: http://dmd.aspetjournals.org/cgi/reprint/27/7/810?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Weber%2C+C&title=A...
Absorption, excretion, and metabolism of the endothelin receptor antagonist bosentan in healthy male subjects
|Published in||Drug Metabolism and Disposition. 1999, vol. 27, no. 7, p. 810-815|
|Abstract||The absorption, excretion, and metabolism of the endothelin receptor antagonist bosentan was investigated in healthy male subjects by administration of 14C-labeled compound. Four subjects received a single oral dose of 500 mg of bosentan (3.7 MBq), and four other subjects received a single i.v. dose of 250 mg of bosentan (3.7 MBq). Radioactivity and concentrations of bosentan and its metabolites were measured in plasma, urine, and feces samples. More than 97% of drug-related material was recovered on average within 3.5 days after oral dosing and within 5 days after i.v. dosing. More than 90% of radioactivity was found in feces after both oral and i.v. dosing. Most of the radioactivity in urine and feces represented bosentan and three metabolites. Ro 48-5033, the major metabolite in plasma, urine, and feces, is the result of hydroxylation at the t-butyl group of bosentan. The two other metabolites Ro 47-8634 and Ro 64-1056 represent minor metabolite species. Ro 47-8634 is the product of O-demethylation of the phenolic methyl ester, and Ro 64-1056 is generated by both demethylation and hydroxylation. The radioactivity in plasma could almost entirely be attributed to bosentan and the two metabolites Ro 48-5033 and Ro 47-8634, whereby both metabolites exhibited much lower plasma levels than bosentan. Hepatic metabolism followed by biliary excretion of the metabolites apparently represents the major pathway of elimination for bosentan in humans.|
|Keywords||Administration, Oral — Antihypertensive Agents/administration & dosage/pharmacokinetics — Area Under Curve — Half-Life — Humans — Injections, Intravenous — Male — Receptors, Endothelin/antagonists & inhibitors — Reference Values — Sulfonamides/administration & dosage/pharmacokinetics|
|WEBER, Cornelia, GASSER, R., HOPFGARTNER, Gerard. Absorption, excretion, and metabolism of the endothelin receptor antagonist bosentan in healthy male subjects. In: Drug metabolism and disposition, 1999, vol. 27, n° 7, p. 810-815. https://archive-ouverte.unige.ch/unige:2334|