How might my in vitro CYP450 inhibition results impact my planning for a preclinical in vivo program?
FDA guidance states, “…if in vitro studies indicate that an investigational drug does not inhibit CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A metabolism, then corresponding in vivo inhibition-based interaction studies of the investigational drug and concomitant medications eliminated by these pathways are not needed.” Note that CYP2A6, CYP2B6, and CYP2E1 “should be considered when appropriate.” – Drug Interaction Studies—Study Design, Data Analysis, and Implications for Dosing and Labeling, Draft Guidance for Industry, US FDA, September 2006.
