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 x body weight (WT)(1.68), 1.15 x 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.
Acosta
E P
EP
Division of Clinical Pharmacology, The University of Alabama at Birmingham, Birmingham, Alabama, USA. eacosta@uab.edu
Brundage
R C
RC
King
J R
JR
Sánchez
P J
PJ
Sood
S
S
Agrawal
V
V
Homans
J
J
Jacobs
R F
RF
Lang
D
D
Romero
J R
JR
Griffin
J
J
Cloud
G
G
Whitley
R
R
Kimberlin
D W
DW
D000284:Administration, Oral; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy; D007275:Injections, Intravenous; D008297:Male; D053719:Tandem Mass Spectrometry; D000077562:Valganciclovir
D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir