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How useful is the ‘cocktail approach’ for evaluating human hepatic drug metabolizing capacity using cytochrome P450 phenotyping probes in vivo?

Relatively selective in vivo substrate probes have been developed for several major CYP isoforms involved in oxidative drug metabolism. There are basically two in vivo methods for identifying the phenotype. One method, the selective (CYP‐specific) phenotyping method, involves administering one single probe drug, whereas the other is a mixed phenotyping or ‘cocktail’ method involving the simultaneous administration of multiple probe drugs, specific for the individual P450. At present, caffeine and chlorzoxazone are used most often as probe drugs for CYP1A2 and CYP2E1, respectively, but these are not necessarily the best probe drugs. Of the potential probe drugs for CYP2C9, CYP2C19, CYP2D6 and CYP3A4, none is really useful. Despite current limitations, the cocktail method for obtaining information about multiple CYP activities in a single experimental session is likely to be more widely used as a screening or phenotyping method for humans in the future.