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Ganciclovir Population Pharmacokinetics in Neonates Following Intravenous Administration of Ganciclovir and Oral Administration of a Liquid Valganciclovir Formulation
Author(s) -
Acosta E P,
Brundage R C,
King J R,
Sánchez P J,
Sood S,
Agrawal V,
Homans J,
Jacobs R F,
Lang D,
Romero J R,
Griffin J,
Cloud G,
Whitley R,
Kimberlin D W
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100150
Subject(s) - valganciclovir , pharmacokinetics , ganciclovir , nonmem , medicine , population , volume of distribution , oral administration , bioavailability , pharmacology , cytomegalovirus , human cytomegalovirus , immunology , human immunodeficiency virus (hiv) , virus , herpesviridae , viral disease , environmental health
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