Individualization of valganciclovir prophylaxis for cytomegalovirus infection in pediatric kidney transplant patients.

Background: Valganciclovir is used for the prophylaxis of cytomegalovirus infection in pediatric solid transplant patients. The current pediatric dose regimen resulted in large variability in drug exposure. A posterior dosage adaptation was required in children to achieve the daily target area under the curve (AUC) of 40-50 mu g.h.mL(-1). However, a clinically feasible tool for valganciclovir dosage adjustment based on individual AUC is not available. The objective of this study was to develop and validate a reliable and clinically applicable limited sampling strategy using Bayesian estimation for individualizing valganciclovir dose in pediatric kidney transplant patients. Methods: The Bayesian estimator to calculate ganciclovir AUC was developed using the original pharmacokinetic dataset consisting of 28 full profiles from 22 pediatric kidney transplant patients. External validation was prospectively performed in an independent validation group consisting of 14 full pharmacokinetic profiles from 14 pediatric kidney transplant patients. Results: The Bayesian estimator of exposure using T0-T2-T4 gave the best predictive performance. The mean prediction error was of 3.1% and Bland-Altman analysis shows that the average difference between referenced and estimated AUCs was 0.4 mu g.h.mL(-1). Conclusion: Valganciclovir dosage adaptation was required in children to achieve target AUC. The Bayesian estimator of valganciclovir, using 3 concentrations measured at T0-T2-T4 after drug intake, was validated and could be used to accurately estimate individual AUC. This approach will be useful for individualizing valganciclovir prophylaxis in pediatric kidney transplant patients.