The metabolism of the 5HT3antagonists ondansetron, alosetron and GR87442 I: A comparison ofin vitroandin vivometabolism andin vitroenzyme kinetics in rat, dog and human hepatocytes, microsomes and recombinant human enzymes

Autor:	J B Houston, G. I. Somers, A. J. Harris, M. K. Bayliss
Rok vydání:	2007
Předmět:	Pharmacology CYP3A4 Health Toxicology and Mutagenesis CYP1A2 General Medicine Metabolism Biology Toxicology Biochemistry In vitro Hydroxylation chemistry.chemical_compound chemistry In vivo Alosetron medicine Microsome medicine.drug
Zdroj:	Xenobiotica. 37:832-854
ISSN:	1366-5928 0049-8254
Popis:	The metabolism of the structurally related 5HT3 antagonists ondansetron, alosetron and GR87442 in the rat, dog and human was determined in hepatocytes, liver microsomes and human recombinant microsomes. The profiles of phase I metabolites were similar in human hepatocytes and microsomes. The metabolites of all three compounds produced in rat, dog and human microsomes and hepatocytes were similar to those seen in vivo, with the major routes of metabolism being N-dealkylation and/or hydroxylation. There was more extensive metabolic processing in hepatocytes than in microsomes; however, sequential metabolism was less extensive in vitro compared with in vivo. The pharmacokinetics of the three 5HT3 antagonists investigated were dominated by CYP3A4 (and/or 2C9) compared with CYP1A2 in man, possibly determined by enzyme capacity rather than relative enzyme affinity. These data support the use of rat, dog and human hepatocytes for the prediction of in vivo metabolites of ondansetron, alosetron and GR87442.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::b6c06921759f42f387c96716f8ffd32e https://doi.org/10.1080/00498250701485575 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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