Limiting cefotaxime pediatric dosing to adult standards: a pharmacokinetic simulation study.
OBJECTIVE
The recommended cefotaxime dose of 50 mg/kg every six to eight hours for pediatric patients with a body weight greater than 20 kg exceeds the standard 1-gram dose recommended for adult patients. This study estimated whether limiting the cefotaxime dose recommended for children with mild to moderate infections to a standard 1-gram dose would achieve serum concentrations and time above the MIC90 comparable to those in adults.


METHODS
Serum concentration profiles were simulated from mean cefotaxime pharmacokinetic parameters that have been published for children and for adults using widely available spreadsheet software. The simulations employed an open, one-compartment, multiple-dose model and were calculated using a common commercial spreadsheet. The model was used to predict serum concentrations using dosage regimens of 1 g or 50 mg/kg administered every six or eight hours in pediatric patients of various weights with pediatric pharmacokinetic parameters and 1 g every six or eight hours for adult patients with adult pharmacokinetic parameters. The time that cefotaxime concentrations exceeded the MIC90 for pediatric pathogens was also calculated.


RESULTS
The 50 mg/kg pediatric dosing regimens administered every 8 hours (q8h) or every 6 hours (q6h) consistently produced peak serum concentrations and area under the concentration versus time curve (AUC) values higher than those in adults. Serum concentrations and AUCs generated for the 1-gram regimens for various pediatric weight categories were also above those predicted in adults. The time above the MIC90 for pediatric patients was equivalent to or exceeded those of the adult simulations for all pathogens.


CONCLUSIONS
The results support the concept of limiting cefotaxime dosage regimens to 1 g administered every 6 or 8 hours for mild to moderate infections in children weighing more than 20 kg. This dosage regimen could lead to dose standardization procedures, which could produce reductions in drug costs associated with individualized dosage preparation.
Dulaney Lopez
A M
AM
Jackson Children's at the University of Miami/Jackson Memorial Medical Center, FL, USA.
Rodriguez
J C
JC
Lopez-Samblas
A M
AM
Estes
K S
KS
D000328:Adult; D019540:Area Under Curve; D002439:Cefotaxime / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002648:Child; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D012015:Reference Standards
D002511:Cephalosporins; D002439:Cefotaxime