Population pharmacokinetics of ganciclovir after valganciclovir in renal transplant children.

Valganciclovir, the ganciclovir prodrug, is an antiviral agent administered orally to prevent or treat cytomegalovirus infection in solid-organ transplant recipients. The valganciclovir dosing regimen in children is still controversial, as the number of patients reaching the area under the concentration-time curve at steady state (AUC(ss)) target (40 to 60 mg.h/liter) remains highly variable. The aim of this study was to determine the population pharmacokinetics of valganciclovir in pediatric renal transplant recipients and propose an appropriate dosing regimen. Children with renal transplant who received valganciclovir to prevent or treat cytomegalovirus infection at the Robert Debre University Hospital were included. Plasma ganciclovir concentrations were determined by high-performance liquid chromatography and UV detection. Population pharmacokinetic analysis was performed with NONMEM software. A total of 104 patients aged 2 to 20 years treated with valganciclovir, administered at a mean dose of 17.3 +/- 6.1 mg/kg of body weight to prevent and/or treat cytomegalovirus infection after renal transplantation, were included. A total of 1,212 samples were available. A two-compartment model with first-order elimination best fitted the data: ganciclovir clearance increased with body surface area, was 15% higher in boys than in girls, and decreased with increasing creatinine concentration. The central volume of distribution increased with body surface area and was 14% higher in boys than in girls. According to the personalized dosing regimen, 65.7% and 65.4% of the children were predicted to achieve the AUC(ss) target for cytomegalovirus prophylaxis and treatment, respectively. A new pharmacokinetic model that allows the proposal of an individualized dose adapted to the characteristics of pediatric patients with renal transplant was built.