Cefotaxime and metabolite disposition in two pediatric continuous ambulatory peritoneal dialysis patients.
OBJECTIVE
To characterize the pharmacokinetics of cefotaxime and desacetylcefotaxime in pediatric patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after intraperitoneal administration of cefotaxime.


METHODS
Case series.


METHODS
Ambulatory children from Children's Hospital nephrology clinic, Columbus, Ohio.


METHODS
Two adolescents without peritonitis.


METHODS
A single intraperitoneal dose of cefotaxime 500 mg per 1 L dianeal was given during CAPD. Cefotaxime and desacetyl-cefotaxime were measured in plasma, urine, and dialysate by HPLC.


RESULTS
Maximum plasma concentration (Cmax) of cefotaxime was 11.94 and 13.08 mg/L and that of desacetylcefotaxime 5.73 and 5.33 mg/L. Time to reach maximum concentration (Tmax) of cefotaxime was 2.22 and 4.08 h, and that of desacetylcefotaxime was 5.33 and 5.73 h after instillation of the intraperitoneal cefotaxime dose. Systemic absorption of cefotaxime was 56.6 and 64.8 percent. Total clearance of cefotaxime was 62 and 79 mL/min/1.73 m2. Nonrenal clearance accounted for nearly 95 percent; renal and CAPD clearance contributed approximately 5 percent of the total clearance. Renal and CAPD clearance measurements of desacetylcefotaxime were similar to those for cefotaxime. Cefotaxime half-life was 1.83 and 2.49 h and desacetylcefotaxime half-life was 8.14 and 11.0 h.


CONCLUSIONS
Cefotaxime was well absorbed and therapeutic serum concentrations were achieved after intraperitoneal administration. Renal and CAPD clearances for cefotaxime and desacetylcefotaxime were low. Cefotaxime nonrenal clearance was unaffected. Further studies are needed to establish appropriate intraperitoneal dosing guidelines of cefotaxime in pediatric CAPD patients.
Paap
C M
CM
College of Pharmacy, University of Texas, Austin.
Nahata
M C
MC
Mentser
M A
MA
Mahan
J D
JD
Puri
S K
SK
Hubbard
J A
JA
D000293:Adolescent; D000465:Algorithms; D002439:Cefotaxime / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D010531:Peritoneal Dialysis, Continuous Ambulatory
C029281:desacetylcefotaxime; D002439:Cefotaxime