Dosing, toxicity and drug concentrations for ganciclovir/valganciclovir in preterm and low birthweight infants treated for cytomegalovirus
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background:
There is a lack of data regarding suitable dosage when administering intravenous ganciclovir (GCV) or oral valganciclovir (valGCV) to preterm and low birthweight infants with cytomegalovirus (CMV) disease.
Methods:
Data were collected for infants born before 32 weeks gestation and/or weighing less than 1.8 kg treated for CMV disease with GCV or valGCV between 2016 and 2023.
Results:
Twenty-four infants (58% males and 48% Asian ethnicity) with a median gestation of 31 weeks [interquartile range (IQR): 26.6–36.1], median weight of 950 g (IQR: 470–1692) and median age of 45 days (IQR: 6–84) at initiation of treatment were included. Seventeen infants were treated for symptomatic postnatal CMV and 7 for symptomatic congenital CMV. Most infants receiving GCV had 6 mg/kg twice daily dosing and most receiving valGCV had 16 mg/kg twice daily dosing. Fourteen infants had drug concentrations measured with combined geometric mean minimum blood plasma concentration (Cmin) of 2.44 mg/L and maximum blood plasma concentration of 7.98 mg/L for doses of 6 mg/kg GCV and 16 mg/kg valGCV, which is higher compared with term infants. The estimated area under the curve at 12 hours (AUC0–12h) was 54.34 mg × h/L, which doubled the value for term infants in a previous study. Notably, AUC0–12h had an inverse relationship with gestational age and weight. Infants with lower gestation and higher Cmin showed a higher tendency for more than 1 adverse effect.
Conclusions:
GCV and valGCV use among preterm and very low birthweight infants with CMV disease resulted in a higher incidence of adverse events, increased AUC0–12h and elevated Cmin compared with term infants. Further pharmacokinetic studies are necessary to determine the ideal dosage in this population.
There is a lack of data regarding suitable dosage when administering intravenous ganciclovir (GCV) or oral valganciclovir (valGCV) to preterm and low birthweight infants with cytomegalovirus (CMV) disease.
Methods:
Data were collected for infants born before 32 weeks gestation and/or weighing less than 1.8 kg treated for CMV disease with GCV or valGCV between 2016 and 2023.
Results:
Twenty-four infants (58% males and 48% Asian ethnicity) with a median gestation of 31 weeks [interquartile range (IQR): 26.6–36.1], median weight of 950 g (IQR: 470–1692) and median age of 45 days (IQR: 6–84) at initiation of treatment were included. Seventeen infants were treated for symptomatic postnatal CMV and 7 for symptomatic congenital CMV. Most infants receiving GCV had 6 mg/kg twice daily dosing and most receiving valGCV had 16 mg/kg twice daily dosing. Fourteen infants had drug concentrations measured with combined geometric mean minimum blood plasma concentration (Cmin) of 2.44 mg/L and maximum blood plasma concentration of 7.98 mg/L for doses of 6 mg/kg GCV and 16 mg/kg valGCV, which is higher compared with term infants. The estimated area under the curve at 12 hours (AUC0–12h) was 54.34 mg × h/L, which doubled the value for term infants in a previous study. Notably, AUC0–12h had an inverse relationship with gestational age and weight. Infants with lower gestation and higher Cmin showed a higher tendency for more than 1 adverse effect.
Conclusions:
GCV and valGCV use among preterm and very low birthweight infants with CMV disease resulted in a higher incidence of adverse events, increased AUC0–12h and elevated Cmin compared with term infants. Further pharmacokinetic studies are necessary to determine the ideal dosage in this population.
Date Issued
2025-04-01
Date Acceptance
2024-09-23
Citation
Pediatric Infectious Disease Journal, 2025, 44 (4), pp.319-325
ISSN
0891-3668
Publisher
Ovid Technologies (Wolters Kluwer Health)
Start Page
319
End Page
325
Journal / Book Title
Pediatric Infectious Disease Journal
Volume
44
Issue
4
Copyright Statement
© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and repro duction in any medium, provided the original work is properly
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40063966
PII: 00006454-202504000-00008
Subjects
Humans
Cytomegalovirus Infections
Male
Antiviral Agents
Valganciclovir
Ganciclovir
Infant, Newborn
Female
Infant, Premature
Infant, Low Birth Weight
Infant
Administration, Oral
Retrospective Studies
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-11-13