Optimizing Donor Number for Consistent Pooled Human Liver Microsomes

Oxidative drug metabolism via the cytochrome P450 (CYP) system is a principle means of drug clearance. Several decades of studies have pointed to five CYP forms—CYP1A2, 2C9, 2C19, 2D6, and 3A—as those which are primarily responsible for human metabolism of small molecule (MW <1500) drugs and drug-like compounds.1 The absolute levels and CYP enzyme activities vary substantially among individual CYP forms and among individuals. This variability has been linked to genetic polymorphisms, disease and exposure to pollutants, drugs, herbal supplements, and other dietary materials which can either increase or decrease levels of individual or groups of CYPs.2,3 In contrast, interindividual CYP activities in animal model species is generally more consistent as these models are inbred and dietary/environmental factors can be rigorously controlled.