Ceftriaxone pharmacokinetics during peritoneal dialysis

Summary The purpose of this study was to investigate the pharmacokinetics of intraperitoneally (IP) administered ceftriaxone (CRO) in patients maintained on chronic peritoneal dialysis. A single 2 g dose of CRO was administered IP to six adult patients who did not have peritonitis at the time of study. After a 5 hour dwell, the peritoneal fluid was exchanged with CRO-free fluid. Exchanges were carried out every 4 to 8 h, over a 24- to 28-h period. The peak total plasma CRO concentration was 104 µg/ml. An average of 74.1% of the IP dose of CRO was absorbed. Plasma protein binding was nonlinear; mean free fraction ranged from 12.8 to 17.9% at low and high concentrations. Dialysate concentrations at the end of subsequent exchanges ranged from means of 19.9 to 2.9 µg/ml. Total CRO clearance from plasma was 10.1 ml·kg^–1·h^–1 and the mean terminal t_1/2 was 12.7 h. Dialytic clearance averaged 0.69 ml·kg^–1·h^–1, only 6.9% of total clearance. A model which incorporates known characteristics of CRO binding and distribution in anuric patients was used to simulate plasma and peritoneal concentrations of CRO during multiple dose IP drug administration.