POPULATION PHARMACOKINETICS OF GANCICLOVIR IN NEWBORNS WITH CONGENITAL CYTOMEGALOVIRUS INFECTIONS

The population pharmacokinetics of ganciclovir was investigated in a g roup of 27 newborns with symptomatic congenital cytomegalovirus infect ion by nonlinear mixed effects modeling analysis. Individual character istics including approximated creatinine clearance from serum (ASCC) a nd body weight (WGE) were identified to significantly influence total clearance from plasma (CL) and the apparent total volume of distributi on (V) of ganciclovir, respectively. The regression equations used to model these relationships were expressed as CL (in liters per hour) = 0.262 + (0.00271 x ASCC) and V (in liters) = 0.627 + (0.437 x WGE). By using this model, typical values of the pharmacokinetic parameter CL and V were 0.428 +/- 0.079 liters/h and 1.773 +/- 0.320 liters, respec tively. Upon validation with a larger number of newborns, this model s hould allow for the definition of possible relationships between the p harmacokinetic disposition of ganciclovir and pharmacodynamic events i n neonates.