Ceftriaxone pharmacokinetics during peritoneal dialysis.

Area of Science:

• Pharmacology
• Nephrology
• Infectious Diseases

Background:

• Chronic peritoneal dialysis (PD) patients often require antibiotic treatment.
• Understanding drug pharmacokinetics in PD is crucial for effective therapy and preventing complications.

Purpose of the Study:

• To investigate the pharmacokinetics of intraperitoneally (IP) administered ceftriaxone (CRO) in patients on chronic peritoneal dialysis.
• To assess CRO absorption, distribution, and elimination in this patient population.

Main Methods:

• A single 2 g dose of ceftriaxone was administered intraperitoneally to six adult patients without peritonitis.
• Peritoneal fluid was exchanged periodically over 24-28 hours, with plasma and dialysate concentrations monitored.
• Pharmacokinetic parameters including peak plasma concentration, absorption percentage, protein binding, and clearance were determined.

Main Results:

• Peak total plasma CRO concentration reached 104 micrograms/ml, with an average absorption of 74.1% of the IP dose.
• Nonlinear plasma protein binding was observed, with mean free fraction varying from 12.8% to 17.9%.
• Dialysate concentrations decreased over time, and total CRO clearance from plasma was 10.1 ml x kg-1 x h-1 with a mean terminal half-life of 12.7 hours.

Conclusions:

• Intraperitoneal ceftriaxone demonstrates significant absorption and prolonged elimination in patients on chronic peritoneal dialysis.
• The pharmacokinetic data suggest that standard dosing may require adjustments in PD patients.
• A simulation model was developed to predict CRO concentrations during multiple IP administrations, aiding in optimized therapeutic regimens.