Linear single‐dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections

The pharmacokinetic characteristics of ganciclovir were determined in neonates (age range, 2 to 49 days) after an 1‐hour intravenous infusion of a single dose of either 4 mg/kg (n = 14) or 6 mg/kg (n = 13). Twenty‐seven newborns with symptomatic cytomegalovirus inclusion disease were enrolled in this open phase I‐II pharmacokinetics, safety, and tolerance trial of ganciclovir at one of two doses. Ganciclovir disposition was best described by a one‐compartment open model with zero‐order input and first‐order elimination. The mean elimination half‐life (t ½ ) for both dose groups was 2.4 hours. The mean apparent volume of distribution (Vd) was 669 ± 70 ml/kg for the 4 mg/kg group and 749 ± 59 ml/kg for the 6 mg/kg group. The mean total body clearance (CL) for the 4 mg/kg and 6 mg/kg groups was 189 ± 28 ml/hr/kg and 213 ± 21 ml/hr/kg, respectively. No significant differences were observed in Vd or CL between the two groups. The Vd, expressed in milliliters, increased with increasing patient weight (r = 0.689; p = 0.0001). The CL, expressed in milliliters per hour per kilogram, increased with increasing age (r = 0.413; p = 0.032). No significant differences were observed between the two dose groups for the area under the curve normalized for dose (AUC/Dose) or the maximum plasma concentration normalized for dose (C max /Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates. Clinical Pharmacology and Therapeutics (1993) 53, 15–21; doi: 10.1038/clpt.1993.4