Experimental Studies of Biliary Excretion of Piperacillin

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Abstract
The nonrecirculating isolated perfused rat liver was used to study biliary antibiotic excretion by the liver in a steady-state, controlled environment in which bile flow, bile salt output, and antibiotic delivery were maintained under constant conditions. The effects of piperacillin, ampicillin, and gentamicin on bile flow and bile salt output were analyzed; none altered bile salt output, and only high concentrations of piperacillin (100 .mu.g/mL) increased bile flow. The ratio of antibiotic concentration in bile and perfusate depended on the type of antibiotic and perfusate concentration. Pipericillin infusions at perfusate concentrations of 50 or 100 .mu.g/mL (in the presence of 60 .mu.M taurocholate) yielded bile to perfusate ratios of 112 .+-. 10 versus 49 .+-. 3, respectively. Using similar perfusate, the concentration ratios for ampicillin (20 .mu.g/mL) and gentamicin (10 .mu.g/mL) were only 3.4 .+-. 0.5 and 0.5 .+-. 0.1, respectively. By altering the perfusate to contain either 60 .mu.M or 240 .mu.M taurocholate, we found variance in bile salt output from 27 .+-. 1 to 115 .+-. 2 .mu.mol/h, yet this alteration had little effect on the output of ampicillin (perfusate concentration of 20 .mu.g/mL), 73 .+-. 7 versus 74 .+-. 12 .mu.g/h, or piperacillin (perfusate concentration 100.mu./mL), 10 .+-. 1 versus 11 .+-. 2 mg/h. Thus, it appears ampicillin and piperacillin are excreted into the bile at high concentrations by bile salt-independent pathways. Partial biliary obstruction (6 cm H2O) results in significant decreases in bile volume. Infusion of 50 .mu.g/mL of piperacillin resulted in increased biliary flow that approached nonobstructed values. Obstruction resulted in significant decreases in bile piperacillin concentration. Whether the choleretic effect of high concentrations of piperacillin has any clinical significance in nonobstructed or obstructed conditions remains to be established.