Population pharmacokinetics of intravenous acyclovir in preterm and term infants.

The Pediatric Infectious Disease Journal
Mario R SampsonBest Pharmaceuticals for Children Act–Pediatric Trials Network

Abstract

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. 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. 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. Acyclovir clearance increased with infant maturation. A dosing strategy based on PMA accounted for developmental changes in acyclovir disposition to achieve the surrogate pharmacodyn...Continue Reading

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Citations

Jul 20, 2014·Advances in Pediatrics·Daniel GonzalezMichael Cohen-Wolkowiez
Nov 5, 2015·Expert Opinion on Drug Metabolism & Toxicology·Elena Yu EnioutinaCatherine M Sherwin
Mar 13, 2016·Contemporary Clinical Trials·Amanda EnglandUNKNOWN Best Pharmaceuticals for Children Act — Pediatric Trials Network Administrative Core Committee
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May 5, 2017·The Journal of Pediatric Pharmacology and Therapeutics : JPPT : the Official Journal of PPAG·John Brock Harris, Amy P Holmes
Apr 9, 2020·Pediatric Emergency Care·Sriram RamgopalTodd A Florin
Sep 18, 2015·The Pediatric Infectious Disease Journal·Irene Ariadne KechagiaAristides Dokoumetzidis
Apr 23, 2020·Neonatal Network : NN·Christopher C McPherson
Oct 10, 2020·Journal of Perinatology : Official Journal of the California Perinatal Association·Laura E MillerRachel G Greenberg
Jun 30, 2021·Journal of Clinical Pharmacology·Jeffrey S BarrettAlexander A Vinks
Oct 12, 2021·Journal of Chemotherapy·Marco Antonio MotisiElena Chiappini

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