Pharmacokinetics of intraperitoneal piperacillin/tazobactam in patients onperitoneal dialysis with and without pseudomonas peritonitis

Objective:The objective of this study was to assess the pharmacokinetics of intraperitoneal (IP) administration of the antibiotic combination piperaci llin/tazobactam (PIP/TAZ) to patients on chronic ambulatory peritoneal dial ysis (CAPD) with and without pseudomonas peritonitis. Design: Open-labeled study. Setting:The study was carried out in the CAPD unit of Assaf Harofeh Medical Center, Zerifin, Israel. Patients and Methods: Six patients participated in the study, 4 had pseudom onas peritonitis, all were given an IP loading dose of 4 g/0.5 g PIP/TAZ. T wenty-four hours after the initial dose, a maintenance dose of 0.5 g/0.0625 g PIP/TAZ was administered with each dialysate exchange for a period of 1 week. The patients without peritonitis received only the loading dose. High performance liquid chromatography was used to determine the concentrations of PIP/TAZ in plasma obtained at 0, 30, 60, 90, 120, 360, 480, 600, 720, a nd 1440 minutes after administration. Samples of the dialysate fluid for de termination of PIP/TAZ concentration were collected at 6, 10, 14, 24, and 7 2, 120, and 168 hours. Results: After the loading dose, the highest plasma PIP concentration (C-ma x) was 51.6 +/- 21.25 mu g/mL and appeared at 1.5 +/- 0.45 hours (t(max)). During the maintenance period plasma PIP concentration was 5.2 +/- 4.75 mu g/mL. Tazobactam was detected in the plasma of 1 patient only The concentra tion of TAZ in the dialysate fluid during the maintenance period was 2.3 +/ - 0.5 mu g/mL. Conclusions: Piperacillin administered IP at 4 g reached plasma concentrati ons comparable to intravenous administration and considered therapeutic (ab ove the MIG,, for Pseudomonas aeruginosa) in CAPD patients with or without peritonitis. The maintenance dose, however, should be augmented. Tazobactam could not be detected in the plasma of most patients and the therapeutic i mplications of IP administration of TAZ cannot be directly correlated to in travenous administration.