Enigbokan M A, Preston J, Hubbard C, Thompson J O
Texas Southern University, College of Pharmacy and Health Sciences, Houston 77004.
Res Commun Chem Pathol Pharmacol. 1994 Mar;83(3):270-8.
The renal handling of two anticancer (a-Ca) pyrimidines 5-fluorodeoxyuridine (FUdR) and 5-fluorouracil (5-FU) was investigated in clearance experiments in CF-1 mice using specific inhibitors of classical renal transport systems. The 5-FU was derived from the metabolism of FUdR. Based on the FUdR:inulin clearance ratio and 5-FU:inulin clearance ratio, it was determined that FUdR was secreted into renal tubules while 5-FU underwent reabsorption. The secretion of FUdR was inhibited by cimetidine and dipyridamole but not by probenecid or phloridzin. While the clearance ratio of 5-FU:inulin was significantly reduced by phloridzin, it (i.e., the ratio) was not affected by cimetidine, dipyridamole, or probenecid. The impact of two calcium channel blockers, diltiazem (DZM) and verapamil (VER), on the renal handling of FUdR and 5-FU was also examined. VER increased the secretion of FUdR without affecting the reabsorption of 5-FU while DZM slightly decreased the secretion of FUdR and prevented the reabsorption of 5-FU. These data suggest that the organic cation carrier and a dipyridamole-sensitive nucleoside transporter are involved in the renal excretion of FUdR; that the renal transport of both FUdR and 5-FU is associated with the calcium channel; and that 5-FU utilizes, at least in part, the glucose transporter for its reabsorption.
在CF-1小鼠的清除实验中，使用经典肾转运系统的特异性抑制剂，研究了两种抗癌（α-Ca）嘧啶——5-氟脱氧尿苷（FUdR）和5-氟尿嘧啶（5-FU）的肾脏处理过程。5-FU源自FUdR的代谢。根据FUdR与菊粉的清除率之比以及5-FU与菊粉的清除率之比，确定FUdR分泌到肾小管中，而5-FU则被重吸收。西咪替丁和双嘧达莫可抑制FUdR的分泌，但丙磺舒或根皮苷则无此作用。虽然根皮苷可显著降低5-FU与菊粉的清除率之比，但该比值不受西咪替丁、双嘧达莫或丙磺舒的影响。还研究了两种钙通道阻滞剂地尔硫䓬（DZM）和维拉帕米（VER）对FUdR和5-FU肾脏处理的影响。VER增加了FUdR的分泌，而不影响5-FU的重吸收，而DZM则略微降低了FUdR的分泌，并阻止了5-FU的重吸收。这些数据表明，有机阳离子载体和双嘧达莫敏感的核苷转运体参与了FUdR的肾脏排泄；FUdR和5-FU的肾脏转运均与钙通道有关；并且5-FU至少部分利用葡萄糖转运体进行重吸收。
