Sequential metabolism of AMG 487, a novel CXCR3 antagonist, results in formation of quinone reactive metabolites that covalently modify CYP3A4 Cys239 and cause time-dependent inhibition of the enzyme.

Henne, Kirk R; Tran, Thuy B; VandenBrink, Brooke M; Rock, Dan A; Aidasani, Divesh K; Subramanian, Raju; Mason, Andrew K; Stresser, David M; Teffera, Yohannes; Wong, Simon G; Johnson, Michael G; Chen, Xiaoqi; Tonn, George R; Wong, Bradley K

Henne, Kirk R; Tran, Thuy B; VandenBrink, Brooke M; Rock, Dan A; Aidasani, Divesh K; Subramanian, Raju; Mason, Andrew K; Stresser, David M; Teffera, Yohannes; Wong, Simon G; Johnson, Michael G; Chen, Xiaoqi; Tonn, George R; Wong, Bradley K.

Afiliação

Henne KR; Department of Pharmacokinetics and Drug Metabolism, Amgen, Inc., 1120 Veterans Blvd., South San Francisco, CA 94080, USA. khenne@amgen.com

Drug Metab Dispos ; 40(7): 1429-40, 2012 Jul.

Article em En | MEDLINE | ID: mdl-22517972

Assuntos

Acetamidas/farmacologia; Acetamidas/farmacocinética; Citocromo P-450 CYP3A/metabolismo; Pirimidinonas/farmacologia; Pirimidinonas/farmacocinética; Receptores CXCR3/antagonistas & inibidores; Biotransformação; Humanos; Redes e Vias Metabólicas; Microssomos Hepáticos/metabolismo; Midazolam/metabolismo; Midazolam/farmacocinética; Oxigênio/metabolismo; Proteólise; Quinonas/farmacocinética; Receptores CXCR3/metabolismo; Testosterona/metabolismo; Testosterona/farmacocinética

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirimidinonas / Citocromo P-450 CYP3A / Receptores CXCR3 / Acetamidas Limite: Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article

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