Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group.
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 (t1/2) 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 (Cmax/Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates.
Department of Pharmacology, University of Alabama, Birmingham 35233.
J M
JM
Trang
L
L
Kidd
W
W
Gruber
G
G
Storch
G
G
Demmler
R
R
Jacobs
W
W
Dankner
S
S
Starr
R
R
Pass
S
S
Stagno
D003404:Creatinine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000151:congenital / Q000378:metabolism*; D005260:Female; D015774:Ganciclovir / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate
D003404:Creatinine; D015774:Ganciclovir