Pharmacokinetic and Pharmacodynamic Assessment of Oral Valganciclovir in the Treatment of Symptomatic Congenital Cytomegalovirus Disease

• Published in: The Journal of infectious diseases Vol. 197; no. 6; pp. 836 - 845
• Main Authors: KIMBERLIN, David W, ACOSTA, Edward P, CLOUD, Gretchen A, LAKEMAN, Fred D, WHITLEY, Richard J, SKNCHEZ, Pablo J, SOOD, Sunil, AGRAWAL, Vish, HOMANS, James, JACOBS, Richard F, LANG, David, ROMERO, Jose R, GRIFFIN, Jill
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15-03-2008; University of Chicago Press
• Subjects: Administration, Oral; Area Under Curve; Biological and medical sciences; Cytomegalovirus; Cytomegalovirus - isolation & purification; Cytomegalovirus Infections - blood; Cytomegalovirus Infections - congenital; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - virology; Drug Administration Schedule; Female; Fundamental and applied biological sciences. Psychology; Ganciclovir - adverse effects; Ganciclovir - analogs & derivatives; Ganciclovir - blood; Ganciclovir - pharmacokinetics; Ganciclovir - pharmacology; Humans; Infant, Newborn; Male; Microbiology; Miscellaneous; Viral Load; Virology; Cytomegalovirus; Purine nucleoside; Valganciclovir; Herpesviridae; Prodrug; Betaherpesvirinae; Congenital disease; Infection; Virus; Treatment; Viral disease; Nucleoside analog; Antiviral; DNA polymerase inhibitor
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/528376

BackgroundIntravenous ganciclovir administered for 6 weeks improves hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system MethodsTwenty-four subjects received antiviral therapy for 6 weeks. Serial pharmacokinetic assessments were performed after administration of valganciclovir oral solution and of intravenous ganciclovir ResultsOn 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 × 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 × 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 ⩾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 ConclusionsIn 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