title: Pharmacokinetics and safety of extemporaneously compounded valacyclovir oral suspension in pediatric patients from 1 month through 11 years of age.
abstract: BACKGROUND
  Valacyclovir provides enhanced acyclovir bioavailability in adults, but limited data are available in children.
  
  
  METHODS
  Children 1 month through 5 years of age with or at risk for herpesvirus infection received a single 25 mg/kg dose of extemporaneously compounded valacyclovir oral suspension (n = 57), whereas children 1 through 11 years of age received 10 mg/kg valacyclovir oral suspension twice daily for 3-5 days (herpes simplex virus infection) (n = 28) or 20 mg/kg 3 times daily for 5 days (varicella-zoster virus infection) (n = 27). Blood samples for pharmacokinetic analysis were collected during the 6 h after the first dose. Safety was monitored throughout the studies.
  
  
  RESULTS
  Dose proportionality in the maximum observed concentration (C(max)) of acyclovir and the area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)) existed across the 10 to 20 mg/kg valacyclovir dose range. For children 2 through 5 years of age, an increase in dose from 20 to 25 mg/kg resulted in near doubling of the C(max) and AUC(0-infinity). Among infants 1 through 2 months of age receiving 25 mg/kg, the mean AUC(0-infinity) and C(max) were higher ( approximately 60% and 30%, respectively) than those among older infants and children receiving the same dose. Valacyclovir oral suspension was well tolerated. No clinically significant trends were noted in clinical chemical, hematologic, or urinalysis values from screening to follow-up.
  
  
  CONCLUSIONS
  Among children 3 months through 11 years of age, the 20 mg/kg dose of this formulation of valacyclovir oral suspension produces favorable acyclovir blood concentrations and is well tolerated. A dosing recommendation cannot be made for infants <3 months of age because of decreased clearance in this age group. Trial registration. ClinicalTrials.gov identifier: NCT00297206 .
authors.affiliation: Department of Pediatrics, University of Alabama, Birmingham, AL 35233, USA. dkimberlin@peds.uab.edu
authors.forename: David W
authors.initials: DW
authors.lastname: Kimberlin
authors.forename: Richard F
authors.initials: RF
authors.lastname: Jacobs
authors.forename: Stephen
authors.initials: S
authors.lastname: Weller
authors.forename: Jan-Stefan
authors.initials: JS
authors.lastname: van der Walt
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Heitman
authors.forename: Choy Y
authors.initials: CY
authors.lastname: Man
authors.forename: John S
authors.initials: JS
authors.lastname: Bradley
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000284:Administration, Oral; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006566:Herpesviridae Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D013535:Suspensions; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D013535:Suspensions; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir