Drug Dosing in Postdilution Hemodiafiltration: Pharmacokinetic Principles and Clinical Implications

Postdilution hemodiafiltration (HDF) combines diffusive and convective transport to enhance solute removal across a broad molecular weight spectrum compared with conventional high-flux hemodialysis. This review summarizes current evidence on drug dosing in patients undergoing HDF, integrating pharmacokinetic principles, available clinical data, and practical considerations for individualized therapy. Drug removal during HDF depends on multiple factors, including molecular weight, protein binding, volume of distribution, membrane characteristics, and treatment-related parameters, such as blood flow, dialysate flow, and convection volume. While the effect of HDF on small solute clearance is generally modest compared with high-flux hemodialysis, convective transport substantially enhances the removal of middle molecules. Estimation of total drug removal provides a framework for postdialysis supplementation, but interpretation must account for postdialysis rebound, particularly for drugs with large volumes of distribution or multicompartment kinetics, where redistribution may attenuate net removal. In this context, reliance on intradialytic clearance alone may overestimate drug elimination. The combined diffusive and convective clearance achieved with HDF can alter drug exposure. Higher elimination should be anticipated for small, water-soluble medications, with dosing individualized using established pharmacokinetic principles and supported by therapeutic drug monitoring. Given the limited availability of HDF-specific pharmacokinetic data, dosing recommendations often rely on extrapolation from hemodialysis studies combined with mechanistic considerations. A structured approach that integrates drug properties, treatment parameters, and clinical context may support safer and more effective medication management in patients receiving HDF.