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Cefotaxime and metabolite disposition in two pediatric continuous ambulatory peritoneal dialysis patients
C M Paap1, M C Nahata, M A Mentser
1College of Pharmacy, University of Texas, Austin.
Insights
Cefotaxime administered intraperitoneally achieved therapeutic levels in pediatric patients on continuous ambulatory peritoneal dialysis (CAPD). Nonrenal clearance was high, with low renal and CAPD clearance, suggesting potential for altered dosing in CAPD.
Area of Science:
- Pharmacology
- Nephrology
- Pediatrics
Background:
- Continuous ambulatory peritoneal dialysis (CAPD) is a treatment for pediatric kidney failure.
- Understanding drug pharmacokinetics in CAPD patients is crucial for effective treatment.
- Cefotaxime is a commonly used antibiotic, but its behavior in CAPD is not well-defined.
Purpose of the Study:
- To determine the pharmacokinetic profile of cefotaxime and its metabolite, desacetylcefotaxime.
- To evaluate the absorption, distribution, metabolism, and excretion of intraperitoneally administered cefotaxime in pediatric CAPD patients.
Main Methods:
- A case series involving two pediatric CAPD patients without peritonitis.
- A single intraperitoneal dose of cefotaxime (500 mg/L) was administered.
- Plasma, urine, and dialysate concentrations of cefotaxime and desacetylcefotaxime were measured using High-Performance Liquid Chromatography (HPLC).
Main Results:
- Cefotaxime demonstrated good systemic absorption (56.6-64.8%) with therapeutic plasma concentrations.
- Nonrenal clearance accounted for approximately 95% of cefotaxime clearance, with low renal and CAPD clearance (around 5%).
- The half-life of cefotaxime was 1.83-2.49 hours, while desacetylcefotaxime had a longer half-life of 8.14-11.0 hours.
Conclusions:
- Intraperitoneal cefotaxime administration in pediatric CAPD patients leads to good absorption and therapeutic serum concentrations.
- Low renal and CAPD clearance suggests that nonrenal pathways are primary for cefotaxime elimination.
- Further research is required to establish optimal intraperitoneal dosing guidelines for cefotaxime in this population.
Objective:
To characterize the pharmacokinetics of cefotaxime and desacetylcefotaxime in pediatric patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after intraperitoneal administration of cefotaxime.
Design:
Case series.
Setting:
Ambulatory children from Children's Hospital nephrology clinic, Columbus, Ohio.
Patient Population:
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.