Population pharmacokinetics of ganciclovir following administration of valganciclovir in paediatric renal transplant patients.

OBJECTIVE: To develop a population pharmacokinetic model for valganciclovir in paediatric renal transplant recipients, identify covariates that explain variability, and determine valganciclovir dosage regimens for cytomegalovirus (CMV) prophylaxis in children.
METHODS: The pharmacokinetics of valganciclovir were described with plasma concentrations from 22 patients (age range 3-17 years) using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment model with lag-time and first-order absorption and elimination was developed. The final model was validated using a bootstrap and visual predictive check. The dosage regimens of valganciclovir for CMV prophylaxis in children were simulated using the final model.
RESULTS: The mean population pharmacokinetic parameters were apparent systemic clearance (CL) 10.1L/h, apparent central volume of distribution 5.2 L, apparent peripheral volume of distribution 30.7 L, inter-tissue clearance 3.97 L/h, absorption rate constant 0.369 h-1 and lag-time 0.743 h. The covariate analysis identified creatinine clearance (CL(CR)) and bodyweight (WT) as individual factors influencing the apparent oral clearance: CL= 8.04 x (CL(CR)/89)(2.93) + 3.62 x (WT/28) L/h. The results of the simulation showed that for a typical patient (WT 28 kg and CL(CR) 89 mL/min), an area under the plasma concentration-time curve of 43 +/- 10.6 mg x h/mL will be achieved with valganciclovir 500 mg once daily.
CONCLUSION: The dosage regimens of valganciclovir for CMV prophylaxis have been defined using the final population pharmacokinetic model based on WT and CLCR for paediatric renal transplantation patients.