Intra-individual variation of drug metabolism by cytochrome P450s in human liver microsomes  

出　　处：《中国药理学通报》2015年第B11期212-212,共1页Chinese Pharmacological Bulletin

摘　　要：Aim To investigate the intra-individual variation in activities of cytochrome P450 enzymes （CYP） in human liver microsomes （HLM）. Methods CYP＇s relative Kin, VmaX and CLi.t （n = 105） expressing as relative metabolic activities （RMAs） and variations of RMAs in 10 CYPs expressing as intra-individual percentage coeffi- cient of variations （ICV） were calculated. Results The ICVs of relative Vmax, K and CLint were 44.03% （16.79% -127.42% ）, 45.88% （18.31% -140. 14% ） and 52.00% （24.20%-134.81% ）. Overall RMAs for 10 CYPs were sorted. The orders, from highest to lowest, were CYP2D6, 1A2, 2C19, C9, 3A4/5, 2B6, 2A6, 2C8 and 2El for K , CYP3A4/5, 2C19, 2D6, 2C8, 2El, 2B6, 1A2, 2A6 and 2C9 for Vmax, CYP2D6, 2B6, 3A4/5, 2C19, 2C9, 1A2, 2El, 2C8 and 2A6 for CLint. CYP2A6＊ 4, CYP2B6 758A 〉 G and 2D6 100C 〉 T contributed to intra-individual variation in activities of CYPs. Conclusion The conception of ＂intra-individual variation＂ in activities of CYPs which means different CYPs presenting different activities of drug metabolism in one person was first put forward. We demonstrated that intra-individual variation in activities of CYPs were very remark- able in normal HLMs for the first time, which built a substantial foundation for the future development of precision medicine.

关 键 词：CYP metabolism intra-individual variation HLM ICV polymorphism 

分 类 号：R[医药卫生]