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

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.