Serum ganciclovir drug exposure in children receiving standard ganciclovir and valganciclovir dosing

Introduction: Intravenous ganciclovir (IV GCV) or its oral prodrug, valganciclovir (VGCV), is used for the prevention and treatment of cytomegalovirus (CMV) infection in immunocompromised children. Studies shown a serum area under the concentration-time curve (AUC24) of ≥ 40mg·h/L is required for effective CMV prevention.

Aims: To determine a population pharmacokinetic model for immunocompromised children, evaluate the serum AUC24 achieved with standard GCV/VGCV dosing and propose an optimised dosing strategy to improve attainment of target drug exposures.

Methods: Retrospective audit of ganciclovir therapeutic drug monitoring data from two hospitals. A paediatric PopPK model was developed using NONMEM and the population AUC24 under standard dosing calculated. An optimised dosing strategy was determined to achieve an AUC24 between 40-100 mg·h/L.

Results: 161 samples from 24 children with a median (range) age of 9.0 years (0.4-17.0) were analysed. A one-compartment model with first-order absorption and elimination with weight and serum creatinine as covariates was developed [1]. The median [90% CI] steady state AUC24 of GCV 5 mg/kg bid was 39.5 mg/L·h [22.2-316.9] with 50% having an AUC24 < 40 mg·h/L. For standard VGCV dosing, 7 × body surface area (BSA) × creatinine clearance (CrCL), AUC24 was 79.6 mg/L·h [41.7-170.6]. An optimised dosing regimen for GCV achieved the therapeutic target in 67-80% of children.

Conclusions: Standard IV GCV dose achieves inadequate serum drug exposure in children and requires optimisation while BSA and CrCL based standard VGCV dose could achieve adequate drug exposure.


[1] EP Acosta, RC Brundage, JR King, PJ Sánchez, S Sood, V Agrawal, et al. Ganciclovir population pharmacokinetics in neonates following intravenous administration of ganciclovir and oral administration of a liquid valganciclovir formulation. Clin Pharmacol Ther 2007;81:867-72.