Ganciclovir Population Pharmacokinetics in Neonates Following Intravenous Administration of Ganciclovir and Oral Administration of a Liquid Valganciclovir Formulation

Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research‐grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty‐four neonates received 6 weeks of antiviral therapy. Ganciclovir and valganciclovir were measured by liquid chromatography/tandem mass spectroscopy. NONMEM version VI beta was used for population analyses. All profiles were consistent with a one‐compartment model. Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 × body weight (WT) 1.68 , 1.15 × WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial‐grade valganciclovir oral solution may be a viable option for administration to neonates. Clinical Pharmacology & Therapeutics (2007) 81 , 867–872. doi: 10.1038/sj.clpt.6100150 ; published online 28 March 2007