Selection of Appropriate Experimental Designs

FIGURE 15.3 Assessment of time linearity using (a) substrate depletion and (b) metabolite formation approaches and (c) confirmation of linearity with respect to protein for the metabolite formation approach. 

2 Chemical/Antibody Inhibition The selectivity of chemical inhibition for cytochrome P450 inhibitors is often dependent on inhibitor concentration. For example, ketoconazole is a potent and selective inhibitor of CYP3A enzymes at 1 xM concentration, whereas at higher concentrations it also inhibits CYP2C8 and other enzymes. A list of selective chemical cytochrome P450 inhibitors is shown in Table 15.1 (Tucker et al., 2001). Note that in 

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. 

4 Quantitative Reaction Phenotyping Using Metabolite Standard In 

---