Population pharmacokinetics of intravenous acyclovir in preterm and term infants.

Journal Article

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 × [postmenstrual age (PMA)/31.3 weeks]. 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.

Full Text

Duke Authors

Cited Authors

  • Sampson, MR; Bloom, BT; Lenfestey, RW; Harper, B; Kashuba, AD; Anand, R; Benjamin, DK; Capparelli, E; Cohen-Wolkowiez, M; Smith, PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network,

Published Date

  • January 2014

Published In

Volume / Issue

  • 33 / 1

Start / End Page

  • 42 - 49

PubMed ID

  • 24346595

Electronic International Standard Serial Number (EISSN)

  • 1532-0987

Digital Object Identifier (DOI)

  • 10.1097/01.inf.0000435509.75114.3d

Language

  • eng

Conference Location

  • United States