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

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 (PK) sampling study. All infants were <32 weeks gestational age and >500 g at enrollment. Plasma for ganciclovir quantitation was collected at steady state at 0, 1, 2-3, 5-7, and 10-12 hours after the dose. Specimens were shipped and analyzed, and PK parameters were calculated in real time. Noncompartmental and modeling approaches were used for analysis. RESULTS: Eighteen infants were enrolled; their mean gestational age at delivery was 26.7 weeks, and their mean age and weight at enrollment were 42 days and 1519.0 g, respectively. PK assessments were completed in 17. The geometric mean dose and resulting 12-hour area under the curve were 5.19 mg/kg and 52.7 mg · h/L, respectively. A total of 85 ganciclovir concentration-time data points were available for modeling. A 1-compartment power covariate model with weight and serum creatinine on clearance and weight on distribution volume was used. Noncompartmental and modeled PK parameters were similar. CONCLUSIONS: These are the first intravenous ganciclovir population PK data with covariate assessments in premature infants being treated for CMV disease. Results suggest an intravenous dose of 5 mg/kg every 12 hours may be an appropriate starting regimen in of premature infants with congenital CMV. Additional data are needed in this and other populations to better define optimal ganciclovir exposure targets.