Population pharmacokinetics of ganciclovir after valganciclovir in renal transplant children.

Abstract

Valganciclovir, the ganciclovir prodrug, is an antiviral agent administered orally to prevent or treat cytomegalovirus infection in solid organ transplant recipients. Dosing regimen of valganciclovir is still controversial in children, as the number of patients reaching the Area Under the Curve at steady state (AUCss) target (40 - 60 mg.h/L) remains highly variable. The aim of this study was to determine the population pharmacokinetics of valganciclovir in paediatric renal transplant recipients and propose an appropriate dosing regimen. Renal transplant children who received valganciclovir to prevent or treat cytomegalovirus infection at Robert Debré University Hospital were included. Plasma ganciclovir concentrations were determined by high performance liquid chromatography and ultraviolet detection. Population pharmacokinetic analysis was performed with NONMEM software. 104 patients, aged 2 to 20 years, treated with valganciclovir administered at a mean dose of 17.3 ± 6.1 mg/kg to prevent and/or treat cytomegalovirus infection after renal transplantation were included. A total of 1212 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 and decreased with increasing creatinine concentration. Central volume of distribution increased with body surface area and was 14% higher in boys. According to the personalized dosing regimen, 65.7% and 65.4% of children were predicted to achieve the AUCss target for cytomegalovirus prophylaxis and treatment, respectively. A new pharmacokinetic model was built allowing to propose individualised dose adapted to renal transplanted paediatric patients characteristics.