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Pediatr Infect Dis J. 2014 Jan;33(1):42-9. doi: 10.1097/01.inf.0000435509.75114.3d.

Population pharmacokinetics of intravenous acyclovir in preterm and term infants.

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1
From the *Duke Clinical Research Institute, Durham; †University of North Carolina, Eshelman School of Pharmacy, Chapel Hill, NC; ‡Wichita Medical Research and Education Foundation, Wichita, KS; §EMMES Corporation, Rockville, MD; and ¶University of California-San Diego, Schools of Medicine and Pharmacy, La Jolla, CA.

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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