PHARMACOKINETICS OF CEFEPIME IN PATIENTS UNDERGOING CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS

The pharmacokinetics of cefepime were studied in 10 male patients receiving continuous ambulatory peritoneal dialysis therapy. Five patients received a single 1,000-mg dose and the other five received a single 2,000-mg dose; all doses were given as 30-min intravenous infusions. Serial plasma, urine, and peritoneal dialysate samples were collected; and the concentrations of cefepime in these fluids were measured over 72 h by using a high-performance liquid chromatographic assay with UV detection. Pharmacokinetic parameters were calculated by noncompartmental methods. The peak concentrations in plasma and the areas under the plasma concentration-versus-time curve for the 2,000-mg dose group were twice as high as those observed for the 1,000-mg dose group. The elimination half-life of cefepime was about 18 h and was independent of the dose. The steady-state volume of distribution was about 22 liters, and values for the 1,000- and 2,000-mg doses were not significantly different. The values for total body clearance and peritoneal dialysis clearance were about 15 and 4 ml/min, respectively. No dose dependency was observed for the clearance estimates. Over the 72-h sampling period, about 26% of the dose was excreted intact into the peritoneal dialysis fluid. For 48 h postdose, mean concentrations of cefepime in dialysate at the end of each dialysis interval exceeded the reported MICs for 90% of bacteria which commonly cause peritonitis resulting from continuous peritoneal dialysis. A parenteral dose of 1,000 or 2,000 mg of cefepime every 48 h would maintain the antibiotic levels in plasma and peritoneal fluid above the MICs for 90% of the most susceptible bacteria for the treatment of systemic and intraperitoneal infections.