Involvement of CYP2C9 and UGT2B7 in the metabolism of zaltoprofen, a nonsteroidal anti-inflammatory drug, and its lack of clinically significant CYP inhibition potential

Autor:	Akio Hiyama, Atsuhiro Inaba, Nobuhiko Kowata, Emiko Kamada, Shigeru Furuta, Michael Hall, Nobuyoshi Akagawa, Anne Matthews, Yoshihiro Kawabata, Tadashi Kurimoto
Rok vydání:	2002
Předmět:	Pharmacology CYP2D6 CYP3A4 biology Chemistry CYP1A2 Cytochrome P450 Drug interaction UGT2B7 In vivo biology.protein Microsome Pharmacology (medical)
Zdroj:	British Journal of Clinical Pharmacology. 54:295-303
ISSN:	0306-5251
Popis:	Aims To identify the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) isoforms responsible for the formation of the primary metabolite(s) of zaltoprofen, and to predict possible drug interactions by investigating the inhibition of CYP isoforms in vitro. Methods The metabolism of zaltoprofen was studied in vitro using recombinant CYP and UGT isoform cDNA-expression systems. The effects of selective isoform inhibitors on zaltoprofen metabolism were studied using human liver microsomes. The inhibitory effects of zaltoprofen on the metabolism of selective probe substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 were also determined in human liver microsomes. Results Zaltoprofen was extensively metabolized by CYP2C9 and UGT2B7. CYP2C9 catalysed sulphoxidation but not hydroxylation of zaltoprofen. In the human liver microsomal metabolism study, zaltoprofen metabolism was markedly inhibited by sulphaphenazole, a selective inhibitor of CYP2C9. In the drug interaction study, negligible inhibition (
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::1b1511ecee7bcf1c3b346ae9287f6d79 https://doi.org/10.1046/j.1365-2125.2002.01649.x Zobrazit plný text záznamu Plný text