Grossie V B, Loo T L
Cancer Treat Rep. 1983 Mar;67(3):253-7.
The effect of induced protein-calorie malnutrition (PCM) and its subsequent nutritional repletion with chow or total parenteral alimentation (TPA) on the hepatobiliary excretion of methotrexate (MTX) was determined in the Sprague-Dawley rat. Compared with full-fed controls, PCM resulted in a decrease in body and liver weight, bile flow, and the cumulative excretion of MTX but a consistently higher plasma MTX concentration at each time-point measured. Repletion with chow and TPA resulted in a gain in body weight and an increase in liver weight. Chow repletion resulted in an increase in bile flow and biliary excretion of MTX equal to that for the controls. Repletion with chow also resulted in a consistently lower plasma MTX concentration as compared with PCM rats. Repletion of PCM via TPA did not affect biliary, or plasma, MTX concentrations although the cumulative biliary excretion of MTX was further decreased. The biliary clearance of MTX was decreased by PCM. The clearance for rats repleted with chow, however, was greater than that for the controls. The clearance for PCM rats repleted via TPA was equal to that for PCM rats but less than that for the controls. When expressed as a function of liver weight and compared with PCM rats, the clearance for rats repleted with chow was increased while that for malnourished rats repleted parenterally was decreased. These studies suggest that the biliary excretion of MTX in the rat is a carrier-mediated process that is sensitive to the nutritional status of the host and independent of the effect of nutritional status on liver weight.
在斯普拉格-道利大鼠中，测定了诱导性蛋白质-热量营养不良（PCM）及其随后用普通饲料或全胃肠外营养（TPA）进行营养补充对甲氨蝶呤（MTX）肝胆排泄的影响。与正常喂食的对照组相比，PCM导致体重和肝脏重量、胆汁流量以及MTX的累积排泄量下降，但在每个测量时间点血浆MTX浓度始终较高。用普通饲料和TPA进行补充导致体重增加和肝脏重量增加。用普通饲料补充导致胆汁流量增加和MTX的胆汁排泄量增加，与对照组相当。与PCM大鼠相比，用普通饲料补充还导致血浆MTX浓度持续降低。通过TPA对PCM进行补充虽然MTX的累积胆汁排泄量进一步下降，但不影响胆汁或血浆MTX浓度。PCM降低了MTX的胆汁清除率。然而，用普通饲料补充的大鼠的清除率高于对照组。通过TPA补充的PCM大鼠的清除率与PCM大鼠相同，但低于对照组。当以肝脏重量的函数表示并与PCM大鼠相比时，用普通饲料补充的大鼠的清除率增加，而经胃肠外补充的营养不良大鼠的清除率降低。这些研究表明，大鼠中MTX的胆汁排泄是一个载体介导的过程，对宿主的营养状况敏感，且独立于营养状况对肝脏重量的影响。
