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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

URL:
http://www.ncbi.nlm.nih.gov/pubmed/24346595

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.

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