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  • Title: Biliary elimination and hepatic disposition of an association of piperacillin and tazobactam: experimental evaluation.
    Author: Brogard JM, Caro-Sampara F, Westphal JF, Blickle JF, Jehl F.
    Journal: Drugs Exp Clin Res; 1994; 20(6):247-55. PubMed ID: 7758397.
    Abstract:
    Biliary elimination and hepatic disposition of tazocillin, an association of a highly bile-excreted ureido-penicillin, piperacillin, with a beta-lactamase inhibitor, tazobactam, have been assessed applying an isolated perfused rabbit liver experimental model. Six investigations were performed, each during a 3 h period, using reconstituted blood circulating in a closed circuit. Piperacillin and tazobactam concentration in all specimens were determined by high performance liquid chromatography. Blood samples and cumulative bile secretion were collected every 30 min, and liver fragments were isolated at the end of each experiment for dosage purposes. Following the simultaneous administration of piperacillin 80 mg and tazobactam 10 mg (dose ratio 8/1) in the perfusion device, theoretical initial serum concentrations were respectively 414 micrograms/ml and 32.1 micrograms/ml. Maximal biliary concentrations of 4431 +/- 1541 (s.d.) of piperacillin and 21.3 +/- 7.8 micrograms/ml of tazobactam were reached between 0.5-1 h and 2.5-3 h, respectively. Cumulative biliary excretion (0-3 h) amounted to 37.6 +/- 17.7% of the administered dose for piperacillin and 1.5% for tazobactam. At the end of the perfusion, respectively 22.1% and 50.7% of piperacillin and tazobactam doses remained in the circulating blood, while 1.1% and 5.6% were found in the liver. On the basis of these data, the calculated percentages of piperacillin and tazobactam doses having undergone hepatic biotransformation, were 6.5% and 1.2%, respectively. Under such experimental conditions, concentrations and excretion of piperacillin in bile prove to be substantial. Of note, tazobactam concentrations turn out to be stable both in serum and in bile whereas they stay at a relatively constant level of 20 micrograms/ml during nearly all the perfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)
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