Single-dose plasma and cerebrospinal fluid pharmacokinetics of ceftriaxone in infants and children.
Pharmacokinetic variables were studied in children with central nervous system infections who received a single dose of ceftriaxone sodium. After initial lumbar puncture of children with documented or suspected bacterial meningitis, ventriculitis, or both, therapy was initiated with i.v. ampicillin and chloramphenicol. Children were randomly selected to receive a single i.v. dose of ceftriaxone. Concentrations of ceftriaxone were measured in plasma at intervals from 0 to 720 minutes after the beginning of the infusion and in cerebrospinal fluid (CSF) at one to five hours after the dose. Blood samples were obtained immediately after the second lumbar puncture for assessment of drug penetration into CSF. Elimination rate constant, elimination half-life, apparent volume of distribution, and plasma clearance were determined from samples obtained 30-720 minutes after the start of the infusion. In two children with ventriculoperitoneal shunts, serial determinations of ceftriaxone in CSF were obtained. All eight children who received 75 mg/kg and five of eight who received 50 mg/kg had positive CSF cultures. Volume of distribution was less after the 50 mg/kg dose than after the 75 mg/kg dose. In the children with shunts, adequate CSF drug concentrations were maintained throughout 12 hours of testing. These data support a 12-hour dosage interval, but clinical studies are needed to evaluate efficacy of the drug at both 12-hour and 24-hour dosage regimens.
D000293:Adolescent; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D002443:Ceftriaxone; D002552:Cerebral Ventricles; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D007700:Kinetics; D008297:Male; D008581:Meningitis / Q000188:drug therapy / Q000382:microbiology; D008826:Microbial Sensitivity Tests
D002443:Ceftriaxone; D002439:Cefotaxime