Renal Function–Guided Valganciclovir Dosing and Ganciclovir Exposure Variability: A Population Pharmacokinetic Simulation Study

Background Ganciclovir (GCV) exposure after standard valganciclovir (VGCV) prophylaxis is highly variable. Guidelines recommend Cockcroft–Gault for renal dose adjustment. We evaluated whether Cockcroft–Gault‐based dosing achieves the target prophylactic exposure (AUC 0‐24h: 40–60 mg.h/L) and whether MDRD or CKD‐EPI alters exposure. Methods Using a validated population pharmacokinetic model, we simulated 10 000 adult solid organ transplant recipients. VGCV doses were assigned according to SmPC renal function categories based on Cockcroft–Gault, MDRD or CKD‐EPI. Patient reclassification, target attainment and exposure around dosing thresholds (25, 40 and 60 mL/min) were assessed. Results MDRD and CKD‐EPI reclassified 45.1% and 39.9% of patients, mostly downward, lowering target attainment (20.1% and 22.7% vs. 30.8% with Cockcroft–Gault). Target attainment never exceeded 40% in any category, and underexposure predominated, reaching up to 94.1% in the most impaired renal function categories. Target attainment was consistently lower just below each threshold, and the 25 and 40 mL/min thresholds were set above the renal function ranges where the corresponding regimens achieved target exposure. Conclusions Renal function category‐based VGCV dosing does not reliably achieve target GCV exposure. Current thresholds are poorly aligned with the exposure‐response relationship and warrant re‐examination. Alternative equations do not reduce the variability, supporting exposure‐guided approaches such as therapeutic drug monitoring and model‐informed precision dosing.