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Population Pharmacokinetics of Intravenous Acyclovir in Preterm and Term Infants

2014 Jan

Journal Article

Authors:
Sampson, M.R.; Bloom, B.T.; Lenfestey, R.W.; Harper, B.; Kashuba, A.D.; Anand, R.; Benjamin, D.K.; Capparelli, E.; Cohen-Wolkowiez, M.; Smith, B.

Secondary:
Pediatr Infect Dis J

Volume:
33

Pagination:
42-9

Issue:
1

PMID:
24346595

DOI:
10.1097/01.inf.0000435509.75114.3d

Keywords:
Acyclovir; Administration, Intravenous; Antiviral Agents; Bayes Theorem; BPCA; Cluster Analysis; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Male

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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