Single-dose ceftriaxone kinetics in the newborn.
Ceftriaxone kinetics were characterized after a single, 2-minute, intravenous infusion of 50 mg/kg to 20 sick infants 1 to 8 days old who weighed 1.78 to 4.36 kg. Plasma binding parameters could be determined by equilibrium dialysis in 16 of the infants, in whom kinetic parameters for free ceftriaxone in plasma were also determined. Compared with corresponding values in adults, the elimination t1/2 was longer in infants (19 and 8.4 hours) because of reduced total systemic clearance (4.48 and 8.51 ml/min/m2). The apparent steady-state volume of distribution was of the same order in infants and adults (5,130 and 5,350 ml/m2). Both renal and nonrenal clearance of free ceftriaxone were reduced in infants, but these decreases were partially offset by an increased free fraction; plasma binding affinity and capacity constants for infants were about half the adult values. The mean fraction of dose excreted unchanged in urine was estimated at 70% in the neonates and 46% in adults. There were no clinically significant correlations between the kinetic parameters and either age since birth or age since conception. The fraction of free ceftriaxone in plasma inversely correlated with age since conception and was lower in female infants, which decreased the systemic clearance and volume of distribution of total drug in the female infants compared with the male infants. Values for the volume of distribution and clearance parameters were not related to body size (weight or body surface area). From our results, a ceftriaxone dosage of 50 to 100 mg/day is recommended during the first week of life for newborn infants who weigh between 1.8 and 4.4 kg. Impaired renal function may require a reduction in dosage.
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine; D002443:Ceftriaxone; D005260:Female; D005919:Glomerular Filtration Rate; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D011485:Protein Binding
D001798:Blood Proteins; D002443:Ceftriaxone; D002439:Cefotaxime