Population Pharmacokinetics of Intravenous Acyclovir in Preterm and Term Infants
01/2014
Journal Article
Authors:
Sampson, M.R.;
Bloom, B.;
Lenfestey, R.;
Harper, B.;
Kashuba, A.;
Anand, R.;
Capparelli, E.;
Cohen-Wolkowiez, M.;
Smith, P.B.;
Network, T.Best Pharm
Secondary:
Pediatr Infect Dis J
Volume:
33
Pagination:
42-49
Issue:
1
Journal:
Pediatr Infect Dis J
PMID:
24346595
URL:
http://www.ncbi.nlm.nih.gov/pubmed/24346595
DOI:
10.1097/01.inf.0000435509.75114.3d.
Keywords:
Acyclovir; Antiviral Agents; Bayes Theorem; Cluster Analysis; Infant
Abstract:
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.
