Pediatric Dosage Calculation: Valganciclovir Pharmacokinetic Profiling in Pediatric Renal Transplant Recipients

Objectives: * Investigate oral doses of valganciclovir administered to pediatric transplant patients. * Calculate pediatric valganciclovir dosages based on body weight. * Calculate pediatric valganciclovir dosages based on the manufacturer�s dosing equation. * Relate valganciclovir doses to patient outcomes post-transplantation. * Calculate and model virtual valganciclovir pharmacokinetic behavior. Methods: * Open-label, single-center, retrospective chart review * Study site: OHSU and Doernbecher Children�s Hospital * Inclusion criteria: pediatric kidney transplant patients who required CMV prophylaxis with oral valganciclovir between 2006 to 2010. No exclusion criteria. * Sample size: all patients who entered the study were considered for the analysis. * Data were collected via computerized medical and prescription records of pediatric kidney transplant patients using valganciclovir for CMV prophylaxis: * Demographic and dosing data: Age, height, weight, serum creatinine (SCr), start and end dates of valganciclovir therapy, and the prescribed valganciclovir doses. * Transplantation (Tx) data: Date of Tx, induction regimen, maintenance immunosuppression regimen, and presence or absence of transplant rejection and graft loss. * Outcomes data: CMV status pre- and post-Tx, BK viral status post-Tx, blood or plasma urea nitrogen, SCr, white blood cell count, hemoglobin, and platelet count. Results: * Two patients (<10%) who received valganciclovir doses that were lower than weight-based or manufacturer�s recommended dosing developed CMV viremia or infection. * Eight patients (38%) developed leukopenia (WBC < 3.0 k/mm3) during valganciclovir therapy, most likely due to chronic immunosuppressive therapy plus excessive valganciclovir dosing. * No patients developed nephrotoxicity or thrombocytopenia during valganciclovir therapy (data not shown). Conclusion: * Following the manufacturer�s recommended valganciclovir dosing schedule can be associated with potential for overexposure, toxicity and greater drug costs compared to weight-based dosing. * Ongoing studies include PK simulation to determine AUC arising from different dosing methods, comparison to target AUC of 40-50 mcg/mL, and evaluating the relationship to outcomes.