title: Assessment of biliary excretion of piperacillin-tazobactam in humans.
abstract: Piperacillin-tazobactam concentrations in serum and bile were measured intraoperatively in 10 patients undergoing cholecystectomy (group 1) and 5 cholecystectomized patients provided with external bile duct drainage (group 2). Each patient received a single intravenous dose of piperacillin at 4 g plus tazobactam at 0.5 g over 30 min. Drug concentrations in both serum and bile were measured by high-performance liquid chromatography. In group 1 patients, serum and bile specimens and gallbladder wall fragments were collected at mean times of 70 and 83 min postinfusion, respectively. The mean concentrations of piperacillin and tazobactam were, respectively, 69.1 +/- 41.5 (standard deviation) and 9.9 +/- 5.1 microg/ml in serum, 630.4 microg/ml (range, 24.8 to 1,194 microg/ml) and 11.8 microg/ml (range, 3.6 to 22 microg/ml) in choledochal bile, 342.3 microg/ml (range, 1.1 to 1,149 microg/ml) and 7.7 microg/ml, (range, 0.2 to 23.1 microg/ml) in gallbladder bile, and 49.3 microg/g (range, 9.7 to 223 microg/g) and 2.9 microg/g (range, 0.1 to 5.9 microg/g) in the gallbladder wall. In group 2 patients, the amounts of drugs recovered in bile drainage obtained over 12 h were 28.4 +/- 18.0 and 1.0 +/- 0.5 mg for piperacillin and tazobactam, respectively. Peak piperacillin and tazobactam concentrations in bile reached 358 +/- 242 and 10.8 +/- 4.2 microg/ml, respectively. Comparison of drug levels in serum and bile suggests an underlying active secretion process for piperacillin elimination into the bile, unlike that of tazobactam. From a therapeutic viewpoint, given the concentrations of tazobactam recorded in bile fluid and tissue, the addition of this beta-lactamase inhibitor to piperacillin therapy might be of interest in the management of biliary tract infections, mostly in patients at risk of mixed aerobic-anaerobic infections due to beta-lactamase-producing organisms.
authors.affiliation: Department of Internal Medicine, Medical B Clinic, University Hospitals of Strasbourg, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Westphal
authors.forename: J M
authors.initials: JM
authors.lastname: Brogard
authors.forename: F
authors.initials: F
authors.lastname: Caro-Sampara
authors.forename: M
authors.initials: M
authors.lastname: Adloff
authors.forename: J F
authors.initials: JF
authors.lastname: Blicklé
authors.forename: H
authors.initials: H
authors.lastname: Monteil
authors.forename: F
authors.initials: F
authors.lastname: Jehl
mesh_terms: D000328:Adult; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D002763:Cholecystectomy; D004322:Drainage; D004791:Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010406:Penicillins / Q000097:blood / Q000493:pharmacokinetics*; D010878:Piperacillin / Q000097:blood / Q000493:pharmacokinetics*; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin