Ganciclovir Dosing in Premature Infants Receiving Treatment for Congenital Cytomegalovirus Infection: Results of a Prospective Pharmacokinetic Study

Edward P. Acosta, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
Inmaculada Aban, Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Kevin J. Ryan, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
Pablo J. Sánchez, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA.
Carina A. Rodriguez, Department of Pediatrics, University of South Florida, Tampa, FL, USA.
José R. Romero, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Sunil K. Sood, Department of Pediatrics, Northwell Health Cohen Children's Medical Center, New Hyde Park, NY, USA.
Nazha Abughali, Department of Pediatrics, Case Western Reserve University and MetroHealth, Cleveland, OH, USA.
Ravit Arav-Boger, Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
Roberta L. DeBiasi, Department of Pediatrics, Children's National Medical Center, George Washington University, Washington D.C., USA.
Gregory A. Storch, Department of Pediatrics, Washington University, St. Louis, MO, USA.
John A. Vanchiere, Department of Pediatrics, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA.
Kalyani Peri, Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Richard J. Whitley, Department of Pediatrics, Microbiology, Medicine, and Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.
David W. Kimberlin, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

Document Type

Journal Article

Publication Date

10-10-2025

Journal

The Journal of infectious diseases

DOI

10.1093/infdis/jiaf528

Keywords

Cytomegalovirus; Ganciclovir; Pharmacokinetics; Premature Infants

Abstract

BACKGROUND: Ganciclovir remains the primary therapeutic for cytomegalovirus (CMV) infections in early infancy, but its pharmacokinetics and dosing in very preterm infants with end-organ CMV disease have not been fully evaluated. METHODS: Premature infants with confirmed CMV infection and receiving ganciclovir as standard of care were enrolled into a pharmacokinetic sampling study. All were <32 weeks gestational age and >500 grams at enrollment. Plasma for ganciclovir quantitation was collected at steady-state at 0, 1, and between 2-3, 5-7, and 10-12 hours post-dose. Specimens were shipped, analyzed, and pharmacokinetic parameters calculated in real-time. Noncompartmental and modeling approaches were used for analysis. RESULTS: Eighteen infants were enrolled; mean gestational age at delivery was 26.7 weeks, and mean age and weight at enrollment were 42 days and 1519.0 grams, respectively. Seventeen completed pharmacokinetic assessments. Geometric mean dose and resulting 12 hour area-under-the-curve (AUC12) were 5.19 mg/kg and 52.7 mgxh/L, respectively. A total of 85 ganciclovir concentration-time data points were available for modeling. A one-compartment power covariate model with weight and serum creatinine on clearance and weight on distribution volume was used. Noncompartmental and modeled pharmacokinetic parameters were similar. CONCLUSIONS: These are the first intravenous ganciclovir population pharmacokinetic data with covariate assessments in premature infants being treated for CMV disease. Results suggest an intravenous dose of 5 mg/kg/dose every 12 hours may be an appropriate starting regimen for treatment of premature infants with congenital CMV. Additional data are needed in this and other populations to better define optimal ganciclovir exposure targets.

Department

Pediatrics

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