Serum concentrations of cefotaxime and its metabolite desacetyl-cefotaxime in infants and children during continuous infusion.
BACKGROUND
Continuous infusion of cefotaxime, as opposed to intermittent infusion, seems to be advantageous for a number of reasons. However, few data exist on pharmacokinetics of cefotaxime and its metabolite in infants and children. As part of a quality assessment program, concentrations of cefotaxime and its metabolite desacetyl-cefotaxime were examined.


METHODS
Infants and children (age 0-17 years) routinely received cefotaxime by continuous intravenous infusion and had blood samples taken on days 1, 3, and 5 after start of therapy. Measurements were performed by high-performance liquid chromatography (HPLC) of cefotaxime and desacetyl-cefotaxime.


RESULTS
Patients receiving a dosage of 100 mg/kg/day had a mean cefotaxime concentration of 24.9 mg/l on day 1, ranging from 0.6 to 182.6 mg/l (N = 222). Cefotaxime concentrations in infants younger than 1 week of age showed the largest variation and significantly decreased on consecutive days (p < 0.001, N = 17), together with a significant drop in the cefotaxime-desacetyl-cefotaxime (cef-des) ratio (p = 0.003, N = 16). Cefotaxime clearance increased significantly during the first days after birth (p = 0.024, N = 16). Patients older than 1 week showed negative and significant correlations of cefotaxime concentrations with calculated glomerular filtration rates (p < 0.0001, N = 73), with no significant change in the cef- des ratio on consecutive days.


CONCLUSIONS
Overall, cefotaxime concentrations varied widely between patients, in particular in those younger than 1 week. Our data suggest that liver metabolism as well as renal excretion contribute to total body clearance of cefotaxime and increase during the first few days of live.
Bertels
R A
RA
Department of Pediatrics, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Semmekrot
B A
BA
Gerrits
G P
GP
Mouton
J W
JW
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002439:Cefotaxime / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004358:Drug Therapy; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate
D000900:Anti-Bacterial Agents; D002439:Cefotaxime