Intraindividual Variation and Correlation of Cytochrome P450 Activities in Human Liver Microsomes.

We systematically studied and explored intraindividual variation and correlation in the activities of cytochrome P450 (CYP) using 105 normal liver samples. The intraindividual percentage coefficients of variation of relative K, V, and CL were 45.9% (18.3-140%), 44.0% (16.8-127%), and 52.0% (24.2-134%). Overall values of relative K, V, and CL for 10 CYPs were sorted. The order, from highest to lowest, was CYP2D6, 3A4/5, 2C19, 2C9, 2B6, 1A2, 2A6, 2C8, and 2E1 for K; CYP3A4/5, 2C19, 2D6, 2C8, 2E1, 2B6, 1A2, 2A6, and 2C9 for V; and CYP2D6, 2B6, 3A4/5, 2C19, 2C9, 1A2, 2E1, 2C8, and 2A6 for CL. CYP2A6*4, 2B6 785A>G, and 2D6 100C>T contributed to intraindividual variation of CYP activities. The correlations and similarities among 10 CYP activities were analyzed, and it was found that the highest correlation and similarity for V, K, and CL occurred between CYP2C9 and 2C8, CYP2C9 and 1A2, and CYP2C9 and 2C8, respectively. In conclusion, CYP activities exhibit considerable intraindividual variation, with some notable correlations, which might be helpful to comprehensively understand the internal connection among CYP activities and to guide the rational use of drugs.