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

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.

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.

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.

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.