Physiologically Based Pharmacokinetic Modeling for Olaparib Dosing Recommendations: Bridging Formulations, Drug Interactions, and Patient Populations.

ABSTRACT: We report physiologically based pharmacokinetic-modeling analyses to determine olaparib (tablet or capsule) drug-drug interactions (DDIs). Verified DDI simulations provided dose recommendations for olaparib coadministration with clinically relevant CYP3A4 modulators to eliminate potential risk to patient safety or olaparib efficacy. When olaparib is given with strong/moderate CYP3A inhibitors, the dose should be reduced to 100/150 mg b.i.d. (tablet), and 150/200 mg b.i.d. (capsule). Olaparib administration is not recommended with strong/moderate CYP3A inducers. No dose reductions are required with weak CYP3A inhibitors/inducers. Olaparib was shown to be a weak inhibitor of CYP3A (1.6-fold increase in exposure of a sensitive CYP3A probe) and to have no effect on P-glycoprotein or UGT1A1 sub

SUBMITTER: Pilla Reddy V 

PROVIDER: S-EPMC6585620 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature