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Published on: July 24, 2016
Population pharmacokinetics of intravenous acyclovir in preterm and term infants
Mario R Sampson1, Barry T Bloom, Robert W Lenfestey
1From 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.
Insights
Acyclovir dosing for infants needs adjustment based on postmenstrual age (PMA). This study developed a dosing strategy to ensure effective acyclovir levels in preterm and term infants, improving herpes infection treatment.
Area of Science:
- Neonatal pharmacology
- Pediatric pharmacokinetics
- Infectious disease treatment in neonates
Background:
- Acyclovir is crucial for treating herpes infections in neonates.
- Current dosing guidelines lack characterization of how infant maturation affects acyclovir disposition.
- Optimizing acyclovir therapy in this vulnerable population is essential.
Purpose of the Study:
- To characterize acyclovir pharmacokinetics and pharmacodynamics in preterm and term infants.
- To develop a maturation-based dosing strategy for acyclovir in neonates.
- To evaluate the achievement of a target acyclovir concentration in infants.
Main Methods:
- Population pharmacokinetic analysis of intravenous acyclovir in infants <31 days postnatal age.
- Collected plasma samples to determine acyclovir concentrations.
- Simulated a final pharmacokinetic model using clinical infant data.
Main Results:
- Acyclovir clearance increased with postmenstrual age (PMA), described by the equation: clearance = 0.305 × (PMA/31.3 weeks).
- This model predicted a 4.5-fold increase in clearance from 25 to 41 weeks PMA.
- The proposed dosing strategy achieved the pharmacodynamic target in 91% of infants, with age-specific recommendations.
Conclusions:
- Infant maturation significantly impacts acyclovir clearance.
- A postmenstrual age-based dosing strategy effectively accounts for developmental changes in acyclovir disposition.
- This approach helps achieve therapeutic acyclovir concentrations in a majority of preterm and term infants.
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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