Population pharmacokinetics of intravenous acyclovir in preterm and term infants.

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.

• Authors: Mario R Sampson, Barry T Bloom, Robert W Lenfestey, Barrie Harper, Angela D Kashuba, Ravinder Anand, Daniel K Benjamin Jr, Edmund Capparelli, Michael Cohen-Wolkowiez, P Brian Smith, Best Pharmaceuticals for Children Act–Pediatric Trials Network
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 33 Issue 1 Pg. 42-9 (Jan 2014) ISSN: 1532-0987 [Electronic] United States
• PMID: 24346595 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• Acyclovir

Topics

• Acyclovir (administration & dosage, blood, pharmacokinetics)
• Administration, Intravenous
• Antiviral Agents (administration & dosage, blood, pharmacokinetics)
• Bayes Theorem
• Cluster Analysis
• Female
• Humans
• Infant
• Infant, Newborn
• Infant, Premature (blood, metabolism)
• Male