Cefotaxime disposition pharmacokinetics during peritoneal dialysis

Area of Science:

• Pharmacology
• Nephrology
• Clinical Pharmacy

Background:

• End-stage renal disease (ESRD) significantly alters drug pharmacokinetics.
• Peritoneal dialysis (PD) is a renal replacement therapy with unique drug removal characteristics.
• Cefotaxime is a third-generation cephalosporin antibiotic commonly used for bacterial infections.

Purpose of the Study:

• To investigate the pharmacokinetics of cefotaxime and its metabolite, des-acetyl-cefotaxime, in ESRD patients undergoing PD.
• To determine if cefotaxime dosage requires modification in patients on PD based on its pharmacokinetic profile.

Main Methods:

• Single intravenous dose of 1000 mg cefotaxime administered to 8 ESRD patients on PD.
• Pharmacokinetic parameters calculated using non-linear least squares regression analysis.
• Plasma and dialysis fluid concentrations of cefotaxime and des-acetyl-cefotaxime were measured.

Main Results:

• The biological half-life of cefotaxime ranged from 2.3 to 8.2 hours.
• Total plasma clearance varied between 11 and 103 ml/min.
• Minimal cefotaxime (1.4%–4.2%) was recovered in the dialysis fluid, indicating limited removal by PD.

Conclusions:

• Cefotaxime pharmacokinetics in ESRD patients on PD are characterized by a moderate half-life and variable clearance.
• The limited removal of cefotaxime into dialysis fluid suggests that standard dosing adjusted for renal function is likely adequate.
• No additional dosage adjustments for cefotaxime are necessary during peritoneal dialysis in uraemic patients.