Population Pharmacokinetics of Intravenous Acyclovir in Preterm and Term Infants

Publication Type
Journal Article
Year of Publication
Sampson, Mario R; Bloom, Barry T; Lenfestey, Robert W; Harper, Barrie; Kashuba, Angela D; Anand, Ravinder; Benjamin, Daniel K; Capparelli, Edmund; Cohen-Wolkowiez, Michael; Smith, P Brian; Best Pharmaceuticals for Children Act–Pediatric Trials Network
Pediatr Infect Dis J
Date Published
2014 Jan
Acyclovir; Administration, Intravenous; Antiviral Agents; Bayes Theorem; BPCA; Cluster Analysis; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Male

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.