BILIARY PHARMACOKINETIC PROFILE OF PIPERACILLIN - EXPERIMENTAL-DATA AND EVALUATION IN MAN

  • 1 November 1990
    • journal article
    • research article
    • Vol. 28  (11) , 462-470
Abstract
The purpose of the present experimental and clinical work is to revisit the biliary pharmacokinetic properties of piperacillin. Whereas the up to now published data result from microbiological assays, This work was realized by high performance liquid chromatography. In the isolated and perfused rabbit liver model (n = 5; 3 h), the biliary level peaked at 1,013 .+-. 305 .mu.g/ml between 30 and 60 min. During the experiments, 56.7% and 10.8% of the administered piperacillin (10 mg) were respectively eliminated in bile and submitted to hepatic biotransformation. In man, a single 2. g i.v. dose was administered to 6 volunteers. The excretion measured in the duodenal fluid was 1,681 .+-. 601 .mu.g in 4 h (0.08 of the administered dose). In cholecystectomized patients (n = 10) provided with a T-drain, the biliary peak concentration was 211 .+-. 64 .mu.g/ml during the 2nd h, and the 24 h biliary elimination was 12,963 .+-. 3,332 .mu.g, representing 0.65% of the administered dose. The hepato-biliary clearance was 0.80 ml/min. On per-operatively collected serum, choledocal bile, gallbladder bile and gallbladder wall samples (n = 10 patients), the concentrations of piperacillin simultaneously measured 1 h after the i.v. administration of 2 g were respectively, 81.7 .+-. 20.5, 382 .+-. 110, 30.8 .+-. 2.5 .mu.g/ml and 10.5 .+-. 2.6 .mu.g/g. In a patient provided with a T-drain, piperacillin was measured by both bioassay and HPLC. Concentrations were identical in serum. In bile and urine, the microbiologically measured concentrations were clearly higher than those measured by HPLC. These data suggest the possibility of an hepatic biotransformation of piperacillin that should lead to the production of active metabolites, the structure of which remains to be elucided.

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