Population Pharmacokinetic Modeling of Niraparib to Assess Different Absorption Models

This publication describes the development of an updated population pharmacokinetic (PopPK) model for niraparib, a PARP inhibitor used in advanced ovarian cancer, using data from six clinical studies and more than 14,000 plasma concentration measurements. By incorporating intensive phase 1 PK sampling data, the researchers refined the drug’s absorption model from a simple lag-time structure to a more mechanistic three-transit-compartment absorption model, resulting in improved characterization of niraparib’s pharmacokinetic profile while maintaining consistent estimates for clearance and distribution. The analysis identified albumin, creatinine clearance, alkaline phosphatase, food intake, and body weight as statistically significant covariates, although most had only modest effects on drug exposure except at extreme values. Overall, the updated model provides a more robust framework for future exposure-response analyses and model-informed drug development applications for niraparib.