Background: Valganciclovir (VGC) is extensively used for cytomegalovirus (CMV) infection treatment and prophylaxis after solid organ transplantation (SOT). Dosing of VGC is controversial in pediatric patients and there are several proposed dosing algorithms. According to the manufacturer, area under the curve (AUC0-24) of 40-60 mcg∙h/mL is a predictive pharmacokinetic parameter of efficacy. However, dosing based on manufacturer recommendations is excessively high and potentially toxic in young children with low body surface area (BSA).
Objective: To prospectively evaluate prophylactic VGC dosing in pediatric SOT recipients.
Methods: Children post SOT receiving prophylactic VGC were prospectively studied in a national center for SOT. VGC daily dose was 17 mg/kg. Clinical and pharmacokinetic parameters were recorded. VGC blood levels were drawn at steady state.
Results: Thirteen children, 6 renal and 7 liver-transplant recipients, were studied. Median age was 7.3 years (inter-quartile range 2.2-11.6 years). Median VGC (IQR) AUC0-24 was 21.0 (17.1-39.8) mcg∙h/mL. Most patients (77%, n=10) had an AUC0-24 under 40 mcg∙h/mL. Only 23% (n=3) achieved an AUC0-24 over 40 mcg∙h/mL. AUC0-24 of children younger than 9 years of age was significantly lower than the manufacturer`s recommended AUC0-24 (p=0.012), and decreased as BSA decreased (R2= 0.76). Manufacturer-recommended dose in our patients is 32.9 (24.6-46.1) mg/kg/dose, significantly higher than in our study (p=0.002). No evidence of CMV disease, seroconversion or hematologic toxicity among our patients. Conclusions: Pediatric SOT patients with low BSA probably need lower doses of VGC. However, larger studies are needed in this population.
