Problems and perspectives of phenotyping for drug-metabolizing enzymes in man

Pronounced interindividual differences in drug disposition are mainly cause d by differences in the activity of liver drug-metabolizing enzymes. These depend on known and unknown covariates, including genetic as well as enviro nmental factors. Phenotyping, i.e. assessment of enzyme activities in vivo after administration of a test dose, seems to be a promising tool for deter mining actual metabolic capacities. Although it is a well-established exper imental approach, phenotyping has not yet found its way into clinical pract ice. Main reasons for this are lack of validation for many probes and assay s used, complicated procedures, invasiveness, semi-quantitative test result s, non-compliance on behalf of the subjects tested, high costs, and lack of prospective clinical studies to assess the benefit of phenotyping for pati ents: Problems and perspectives of phenotyping are exemplified for the cyto chrome P-450 enzymes CYP1A2 and CYP3A4, two major human drug-metabolizing e nzymes.