Ma. Enigbokan et al., CHARACTERIZATION OF AND THE INFLUENCE OF CALCIUM-CHANNEL BLOCKERS ON THE RENAL EXCRETION OF PYRIMIDINE ANTICANCER AGENTS, Research communications in chemical pathology and pharmacology, 83(3), 1994, pp. 270-278
The renal handling of two anticancer (a-Ca) pyrimidines 5-fluorodeoxyu
ridine (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. B
ased on the FUdR:inulin clearance ratio and 5-FU:inulin clearance rati
o, it was determined that FUdR was secreted into renal tubules while 5
-FU underwent reabsorption. The secretion of FUdR was inhibited by cim
etidine and dipyridamole but not by probenecid or phloridzin. While th
e clearance ratio of 5FU:inulin was significantly reduced by phloridzi
n, 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 a
lso examined. VER increased the secretion of FUdR without affecting th
e reabsorption of 5-FU while DZM slightly decreased the secretion of F
UdR and prevented the reabsorption of 5-FU. These data suggest that th
e organic cation carrier and a dipyridamole-sensitive nucleoside trans
porter are involved in the renal excretion of FUdR; that the renal tra
nsport of both FUdR and 5-FU is associated with the calcium channel; a
nd that 5-FU utilizes, at least in part, the glucose transporter for i
ts reabsorption.