Evaluation of Cytochrome P450 Inhibition in the 7-in-1 Cocktail Using Preferred Substrates Recommended by Regulatory Agencies

An investigational drug's potential to inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A should be evaluated as recommended by regulatory agencies such as FDA and PMDA. The selection of the probe substrate for the aforementioned CYPs is the first step for in vitro experiments. Numerous combinations of substrates have been characterized in previously reported substrate cocktails in vitro screening assays to evaluate the inhibitory potency of the compound of interest. However, not all of the substrates in the 7-in-1 cocktail were the preferred substrates. The objective of this presentation was to design and introduce a 7-in-1 cocktail approach with each of the substrates being the preferred ones recommended by the regulatory agencies.