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Expression of Bama Minipig and Human CYP3A Enzymes: Comparison of the Catalytic Characteristics with Each Other and Their Liver Microsomes.
Bian, Yicong; Yao, Qingqing; Shang, Haitao; Lei, Jinxiu; Hu, Haihong; Guo, Kenan; Jiang, Huidi; Yu, Lushan; Wei, Hong; Zeng, Su.
Afiliação
  • Bian Y; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Yao Q; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Shang H; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Lei J; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Hu H; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Guo K; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Jiang H; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Yu L; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Wei H; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
  • Zeng S; Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affilia
Drug Metab Dispos ; 43(9): 1336-40, 2015 Sep.
Article em En | MEDLINE | ID: mdl-26070839
ABSTRACT
Minipigs represent a good animal model because of the physiologic and anatomic similarities they share with humans. Three cytochrome P450 (CYP) 3A isozymes, CYP3A22, CYP3A29, and CYP3A46, have recently been reported to be expressed in Bama minipigs, which have limited data relating to their metabolic characteristics. In the present study, Bama minipig CYP3A22, CYP3A29, and CYP3A46 were recombinantly expressed and their metabolic manners were compared with those of human CYP3A4 and CYP3A5 and also human and Bama minipig liver microsomes. The results indicated Bama minipigs and human CYP3A enzymes showed similar metabolic kinetics and metabolite profiles using testosterone, midazolam, and nifedipine as substrates. However, the differences in amino acid sequences change the elimination velocity and metabolic preference of CYP3A enzymes to their substrates. It was demonstrated that CYP3A29, CYP3A4, and CYP3A5 were the most active enzymes for all reactions, whereas CYP3A46 was the least active enzyme. Substrate-dependent metabolism characteristics between human and Bama minipig CYP3A isoenzymes exist.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article