Validation of Time-Dependent Cytochrome P450 Inhibition assays: Use of Stable - Labeled Isotope Internal Standards for Optimal Quantitation

Time-dependent inhibition of cytochrome P450 (CYP) metabolism can lead to nonlinear pharmacokinetics and drug-drug interactions. Recent guidance from the USFDA and drug failures attributable to toxicity that may have a basis in time-dependent inhibition, have elevated interest in this long-known undesirable property of drug candidates.