title: Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease.
abstract: BACKGROUND
  Intravenous ganciclovir administered for 6 weeks improves hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system.
  
  
  METHODS
  Twenty-four subjects received antiviral therapy for 6 weeks. Serial pharmacokinetic assessments were performed after administration of valganciclovir oral solution and of intravenous ganciclovir.
  
  
  RESULTS
  On the basis of a previous pharmacokinetic study of the use of intravenous ganciclovir in this population, a target AUC12 (area under the concentration-time curve over a 12-h period) of 27 mg x h/L was defined. The median dose of oral valganciclovir administered in the present trial was 16 mg/kg, which produced a geometric mean AUC12 of 27.4 mg x h/L. The bioavailability of valganciclovir was 41.1%. Of the 18 subjects who had detectable CMV in whole blood at baseline or during therapy, 11 had <4 log viral DNA copies/mL at baseline, and 7 had > or =4 log viral DNA copies/mL at baseline; subjects who started the study with the higher viral burden experienced greater decreases in viral load but did not clear virus during the 42-day course of therapy. Neutropenia of grade 3 or 4 developed in 38% of subjects.
  
  
  CONCLUSIONS
  In neonates with symptomatic congenital CMV disease, valganciclovir oral solution provides plasma concentrations of ganciclovir comparable to those achieved with administration of intravenous ganciclovir. The results of the present study cannot be extrapolated to extemporaneously compounded liquid formulations of valganciclovir.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA. dkimberlin@peds.uab.edu
authors.forename: David W
authors.initials: DW
authors.lastname: Kimberlin
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Sánchez
authors.forename: Sunil
authors.initials: S
authors.lastname: Sood
authors.forename: Vish
authors.initials: V
authors.lastname: Agrawal
authors.forename: James
authors.initials: J
authors.lastname: Homans
authors.forename: Richard F
authors.initials: RF
authors.lastname: Jacobs
authors.forename: David
authors.initials: D
authors.lastname: Lang
authors.forename: Jose R
authors.initials: JR
authors.lastname: Romero
authors.forename: Jill
authors.initials: J
authors.lastname: Griffin
authors.forename: Gretchen A
authors.initials: GA
authors.lastname: Cloud
authors.forename: Fred D
authors.initials: FD
authors.lastname: Lakeman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitley
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000151:congenital / Q000188:drug therapy* / Q000821:virology; D004334:Drug Administration Schedule; D005260:Female; D015774:Ganciclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D000077562:Valganciclovir; D019562:Viral Load
chemical_list: D000077562:Valganciclovir; D015774:Ganciclovir