Population Pharmacokinetics of intravenous and oral Acyclovir and oral Valacyclovir in pediatric population to optimize dosing regimens.

Context Acyclovir is an antiviral currently used for prevention and treatment of herpes simplex virus (HSV) and varicella-zona virus (VZV) infections. This study aimed to characterize pharmacokinetics of acyclovir and its oral prodrug valacyclovir to optimize dosing in children. Method Children receiving acyclovir or valacyclovir were included in this study. Pharmacokinetics (PK) were described using the non-linear mixed-effect modelling. Dosing simulations were used to obtain trough concentrations above 50% inhibitory concentration for HSV or VZV (0.56mg/L and 1.125mg/L respectively) and maximal peak concentrations below 25 mg/L. Results A total of 79 children (212 concentration-time observations) were included, 50 were taking IV acyclovir, 22 oral and 7 both IV and oral, 57 for preventive and 22 for curative purposes. A one-compartment model with first-order elimination best described the data. An allometric model was used to describe body weight effect and estimated glomerular filtration rate (eGFR) was significantly associated with acyclovir eliminationConclusion: To obtain target maximal and trough concentrations, the more suitable initial acyclovir IV dose was 10 mg/kg/6h for children with normal renal function (eGFR ≤ 250 mL/min/1.73m2) and 15 to 20 mg/kg/6h for children with ARC. (eGFR > 250 mL/min/1.73m2) The 20 mg/kg/8h for acyclovir and valacyclovir produced effective concentrations in more than 75% of children, however a 15 mg/kg/6h, if possible, should be preferred. These doses should be prospectively confirmed and a therapeutic drug monitoring could be used to refine them individually.