Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease.
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.
Kimberlin
David W
DW
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA. dkimberlin@peds.uab.edu
Acosta
Edward P
EP
Sánchez
Pablo J
PJ
Sood
Sunil
S
Agrawal
Vish
V
Homans
James
J
Jacobs
Richard F
RF
Lang
David
D
Romero
Jose R
JR
Griffin
Jill
J
Cloud
Gretchen A
GA
Lakeman
Fred D
FD
Whitley
Richard J
RJ
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
D000077562:Valganciclovir; D015774:Ganciclovir