title: 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.affiliation: 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.
authors.forename: Mario R
authors.initials: MR
authors.lastname: Sampson
authors.forename: Barry T
authors.initials: BT
authors.lastname: Bloom
authors.forename: Robert W
authors.initials: RW
authors.lastname: Lenfestey
authors.forename: Barrie
authors.initials: B
authors.lastname: Harper
authors.forename: Angela D
authors.initials: AD
authors.lastname: Kashuba
authors.forename: Ravinder
authors.initials: R
authors.lastname: Anand
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin
authors.forename: Edmund
authors.initials: E
authors.lastname: Capparelli
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen-Wolkowiez
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D061605:Administration, Intravenous; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000378:metabolism*; D008297:Male
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir