Assessment of Liver Metabolic Function Implications

Summary Inter- and intraindividual variability in pharmacokinetics of most drugs is largely determined by variable liver function as described by parameters of hep­ atic blood flow and metabolic capacity. These parameters may be altered as a result of disease affecting the liver, genetic differences in metabolising enzymes, and various types of drug interactions, including enzyme induction, enzyme in­ hibition or down-regulation. With the now known large number of drug metabolising enzymes, their dif­ ferential substrate specificity, and their differential induction or inhibition, each test substance of liver function should be used as a probe for its specific metabo­ lising enzyme. Thus, the concept of model test-substances providing general in­ formation about liver function has severe limitations . To test the metabolic activity of several enzymes, either several test substances may be given (cocktail ap­ proach) or several metabolites of a single test substance may be analysed (meta­ bolic fingerprint approach). The enzyme-specific analysis of liver function results in a preference for analysis of the metabolites rather than analysis of the clearance of the parent test substance.