Arimori K, Nakano M
Department of Pharmacy, Kumamoto University Hospital, Japan.
J Pharmacobiodyn. 1988 Jan;11(1):1-8. doi: 10.1248/bpb1978.11.1.
The characteristics of exsorption and/or excretion of furosemide into the small intestinal lumen in rats with acute renal failure (ARF rat) were investigated by an in situ single-pass perfusion technique. The amount of furosemide, which was exsorbed into the intestinal lumen after an intravenous administration of the drug to rats was only very slight. The exsorption rate of the drug was significantly increased in ARF rats as compared with normal rats. The average amount of the drug exsorbed into the perfusate in normal rats was 0.83% of dose, whereas that in ARF rats was 1.83% of dose. The amounts of furosemide excreted into the bile in normal rats and ARF rats were 1.53% and 2.64%, respectively. The increased exsorption of furosemide in ARF rats appeared to be due primarily to the decreased binding of the drug to the serum protein, because only the unbound drug permeates through the intestinal membrane into the gastrointestinal (g.i.) tract, and, to some extent, to the increased nonrenal excretion caused by poor renal excretion. Oral activated charcoal had little effect on the serum furosemide levels after intravenous administration of the drug at a dose of 10 mg/kg in ARF rats. The lack of effect of activated charcoal on the elimination of the drug may be due to the small amount of the drug excreted into the g.i. tract.
采用原位单通道灌注技术，研究了急性肾衰竭大鼠（ARF大鼠）中呋塞米向小肠肠腔的外排和/或排泄特征。给大鼠静脉注射呋塞米后，进入肠腔的呋塞米量非常少。与正常大鼠相比，ARF大鼠中该药物的外排率显著增加。正常大鼠灌注液中外排药物的平均量为剂量的0.83%，而ARF大鼠中为剂量的1.83%。正常大鼠和ARF大鼠中排入胆汁的呋塞米量分别为1.53%和2.64%。ARF大鼠中呋塞米外排增加似乎主要是由于药物与血清蛋白结合减少，因为只有未结合的药物才能透过肠膜进入胃肠道，并且在一定程度上是由于肾脏排泄不良导致非肾脏排泄增加。在ARF大鼠中静脉注射10mg/kg剂量的呋塞米后，口服活性炭对血清呋塞米水平几乎没有影响。活性炭对药物消除缺乏作用可能是由于排入胃肠道的药物量较少。
