TICARCILLIN-CLAVULANIC ACID PHARMACOKINETICS IN PRETERM NEONATES WITHPRESUMED SEPSIS

The objective of the reported study was to characterize the pharmacoki netics of ticarcillin and clavulanic acid in premature low-birth-weigh t (less than 2,200 g) neonates with presumed sepsis. Eleven infants re ceived 12 courses of ticarcillin-clavulanic acid at 75 mg/kg of body w eight intravenously every 12 h. Blood samples were collected at 0.5, 1 .5, 4, and 8 h following the infusion of the initial dose. The concent rations of ticarcillin and clavulanic acid were determined by a microb iologic assay. Median (interpatient coefficients of variation) values for the volume of the central compartment, total steady-state volume, distributional clearance, total clearance, and terminal elimination ha lf-life for ticarcillin were 0.030 liter/kg (21%), 0.26 liter/kg (48%) , 0.41 liter/h/kg (47%), 0.047 liter/h/kg (47%), and 4.2 h (45%), resp ectively. For clavulanic acid the parameters were 0.28 liter/kg (32%), 0.36 liter/kg (34%), 11 liters/h/kg (36%), 0.12 liters/h/kg (72%), an d 1.95 h (40%), respectively. Our results suggest that the current dos ing recommendations of 75 mg/kg every 12 h risk subtherapeutic clavula nic acid concentrations and that 50 mg/kg every 6 h is a more rational dosing strategy.