addition to the five major listed cytochrome P450s (CYP1A2, CYP2C9,
CYP2C19, CYP2D6, and CYP3A), the other listed inhibitors include CYP2C8
(substrates include rosiglitazone and some oncology compounds) and CYP2A6
(substrates include coumarin type compounds).
Cytochrome P450-selective antibodies are also commercially available. They
offer increased selectivity over some of the chemical inhibitors, however cost
may prohibit their routine use at earlier stages of drug discovery.
FIGURE 15.4 Use of the substrate depletion approach for assessing potential
contribution to clearance. (a) Recombinant CYP1A2 is depleting parent drug and (b)
both recombinant CYP1A2 and CYP2C9 are depleting parent drug.
496 REACTION PHENOTYPING