Pharmacokinetics of intraperitoneal piperacillin/tazobactam in patients on peritoneal 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 piperacillin/tazobactam (PIP/TAZ) to patients on chronic ambulatory peritoneal dialysis (CAPD) with and without pseudomonas peritonitis.


METHODS
Open-labeled study.


METHODS
The study was carried out in the CAPD unit of Assaf Harofeh Medical Center, Zerifin, Israel.


METHODS
Six patients participated in the study, 4 had pseudomonas peritonitis, all were given an IP loading dose of 4 g/0.5 g PIP/TAZ. Twenty-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 PIPITAZ in plasma obtained at 0, 30, 60, 90, 120, 360, 480, 600, 720, and 1440 minutes after administration. Samples of the dialysate fluid for determination of PIP/TAZ concentration were collected at 6,10,14, 24, and 72, 120, and 168 hours.


RESULTS
After the loading dose, the highest plasma PIP concentration (Cmax) was 51.6 t 21.25 Lig/mL and appeared at 1.5 = 0.45 hours (t,,a). During the maintenance period plasma PIP concentration was 5.2 t 4.75 Lg/mL. Tazobactam was detected in the plasma of 1 patient only. The concentration of TAZ in the dialysate fluid during the maintenance period was 2.3 t 0.5 ig/mL.


CONCLUSIONS
Piperacillin administered IP at 4 g reached plasma concentrations comparable to intravenous administration and considered therapeutic (above the MIC90 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 implications of IP administration of TAZ cannot be directly correlated to intravenous administration.
Zaidenstein
R
R
Department of Internal Medicine A, Assaf Harofeh Medical Center, Zerifin, Israel. Golik@asaf.health.gov.il
Weissgarten
J
J
Dishi
V
V
Koren
M
M
Soback
S
S
Gips
M
M
Averbuch
Z
Z
Simantov
R
R
Assulin
E
E
Golik
A
A
D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010406:Penicillins / Q000493:pharmacokinetics*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010538:Peritonitis / Q000378:metabolism* / Q000382:microbiology*; D010878:Piperacillin / Q000493:pharmacokinetics*; D011552:Pseudomonas Infections / Q000378:metabolism*; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
D010406:Penicillins; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin