【摘 要】
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Aim To investigate the intraindividual variation in activities of cytochrome P450 enzymes (CYP) in human liver microsomes (HLM).Methods GYP s relative Km, Vmax and GLint (n =105) expressing as relativ
【机 构】
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Institute of Clinical Pharmacology,Zhengzhou University,Zhengzhou 450052,China
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Aim To investigate the intraindividual variation in activities of cytochrome P450 enzymes (CYP) in human liver microsomes (HLM).Methods GYP s relative Km, Vmax and GLint (n =105) expressing as relative metabolic activities (RMAs) and variations of RMAs in 10 GYPs expressing as intraindividual percentage coefficient of variations (ICV) were calculated.Results The ICVs of relative Vmax, Km and GLint were 44.03%(16.79% ~ 127.42%), 45.88% (18.31% ~ 140.14%) and 52.00% (24.20% ~ 134.81%).Overall RMAs for 10 GYPs were sorted.The orders, from highest to lowest, were CYP2D6, 1A2, 2C19, C9, 3A4/5, 2B6,2A6, 2C8 and 2E1 for Km, CYP3A4/5, 2C19, 2D6, 2C8, 2E1, 2B6, 1A2, 2A6 and 2C9 for Vmax, CYP2D6,2B6, 3A4/5, 2C19, 2C9, 1A2, 2E1, 2C8 and 2A6 for CLint.CYP2A6 * 4, CYP2B6 758A > G and 2D6 100C >T contributed to intraindividual variation in activities of GYPs.Conclusion The conception of "intraindividual variation" in activities of CYPs which means different GYPs presenting different activities of drug metabolism in one person was first put forward.We demonstrated that intraindividual variation in activities of CYPs were very remarkable in normal HLMs for the first time, which built a substantial foundation for the future development of precision medicine.
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