Population Pharmacokinetics of Intravenous Acyclovir in Preterm and Term Infants.
Sampson, Mario R. PharmD *+; Bloom, Barry T. MD ++; Lenfestey, Robert W. MD, MHS *; Harper, Barrie BSMT (ASCP) *; Kashuba, Angela D. PharmD +; Anand, Ravinder PhD [S]; Benjamin, Daniel K. Jr MD, PhD, MPH *; Capparelli, Edmund PharmD *[P]; Cohen-Wolkowiez, Michael MD, PhD *; Smith, P. Brian MD, MPH, MHS *; on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network
Pediatric Infectious Disease Journal.
33(1):42-49, January 2014.
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Background: Acyclovir is used to treat herpes infections in preterm and term infants; however, the influence of maturation on drug disposition and dosing requirements is poorly characterized in this population.
Methods: We administered intravenous acyclovir to preterm and term infants <31 days postnatal age and collected plasma samples. We performed a population pharmacokinetic analysis. The primary pharmacodynamic target was acyclovir concentration >=3 mg/L for >=50% of the dosing interval. The final model was simulated using infant data from a clinical database.
Results: The analysis included 28 infants (median 30 weeks gestation). Acyclovir pharmacokinetics was described by a 1-compartment model: clearance (L/h/kg) = 0.305 x [postmenstrual age (PMA)/31.3 weeks]3.02. This equation predicts a 4.5-fold increase in clearance from 25 to 41 weeks PMA. With proposed dosing, the pharmacodynamic target was achieved in 91% of infants: 20 mg/kg every 12 hours in infants <30 weeks PMA; 20 mg/kg every 8 hours in infants 30 to <36 weeks PMA and 20 mg/kg every 6 hours in infants 36-41 weeks PMA.
Conclusions: Acyclovir clearance increased with infant maturation. A dosing strategy based on PMA accounted for developmental changes in acyclovir disposition to achieve the surrogate pharmacodynamic target in many infants.
(C) 2014 by Lippincott Williams & Wilkins, Inc.