Calhoun P, Brown K B, Strunk R, Krusch D A, Scheld W M, Hanks J B
Ann Surg. 1987 Apr;205(4):420-7. doi: 10.1097/00000658-198704000-00013.
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 micrograms/mL) increased bile flow. The ratio of antibiotic concentration in bile and perfusate depended on the type of antibiotic and perfusate concentration. Piperacillin infusions at perfusate concentrations of 50 or 100 micrograms/mL (in the presence of 60 microM taurocholate) yielded bile to perfusate ratios of 112 +/- 10 versus 49 +/- 3, respectively. Using similar perfusate, the concentration ratios for ampicillin (20 micrograms/mL) and gentamicin (10 micrograms/mL) were only 3.4 +/- 0.5 and 0.5 +/- 0.1, respectively. By altering the perfusate to contain either 60 microM or 240 microM taurocholate, we found variance in bile salt output from 27 +/- 1 to 115 +/- 2 mumol/h, yet this alteration had little effect on the output of ampicillin (perfusate concentration of 20 micrograms/mL), 73 +/- 7 versus 74 +/- 12 micrograms/h, or piperacillin (perfusate concentration 100 micrograms/mL), 10 +/- 1 versus 11 +/- 2 mg/h. Thus, it appears ampicillin and piperacillin are excreted into 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 micrograms/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.
非循环式离体灌注大鼠肝脏被用于在稳态、可控环境中研究肝脏的胆汁抗生素排泄情况，在此环境下胆汁流量、胆盐输出量以及抗生素输送量均维持在恒定条件。分析了哌拉西林、氨苄西林和庆大霉素对胆汁流量和胆盐输出量的影响；它们均未改变胆盐输出量，只有高浓度的哌拉西林（100微克/毫升）增加了胆汁流量。胆汁中抗生素浓度与灌注液中抗生素浓度的比值取决于抗生素类型和灌注液浓度。在灌注液浓度为50或100微克/毫升（存在60微摩尔牛磺胆酸盐）的情况下输注哌拉西林，胆汁与灌注液的比值分别为112±10和49±3。使用相似的灌注液，氨苄西林（20微克/毫升）和庆大霉素（10微克/毫升）的浓度比值分别仅为3.4±0.5和0.5±0.1。通过改变灌注液使其含有60微摩尔或240微摩尔牛磺胆酸盐，我们发现胆盐输出量从27±1微摩尔/小时变化至115±2微摩尔/小时，但这种改变对氨苄西林（灌注液浓度20微克/毫升）的输出影响不大，分别为73±7微克/小时和74±12微克/小时，对哌拉西林（灌注液浓度100微克/毫升）的输出影响也不大，分别为10±1毫克/小时和11±2毫克/小时。因此，氨苄西林和哌拉西林似乎通过不依赖胆盐的途径以高浓度排泄到胆汁中。部分胆管梗阻（6厘米水柱）会导致胆汁量显著减少。输注50微克/毫升的哌拉西林会使胆汁流量增加，接近未梗阻时的值。梗阻会导致胆汁中哌拉西林浓度显著降低。高浓度哌拉西林的利胆作用在未梗阻或梗阻情况下是否具有任何临床意义仍有待确定。
