Abstract
Guanidinosuccinic acid (GSA) is a uremic toxin, and its excess accumulation in the CSF under uremic conditions is thought to produce neural excitotoxicity. It is important to understand the manner of GSA distribution/elimination from the circulating blood and CSF and its alteration in the presence of renal failure. The purpose of this study was to evaluate the kinetics of GSA in the circulating blood using a rat model of cisplatin-induced renal failure and GSA transport between the circulating blood and CSF. The AUCinf and t1/2 of GSA in cisplatin-treated rats were approximately 7-fold greater than those in normal rats. The CLtot of GSA in cisplatin-treated rats was reduced by 88% compared with normal rats, whereas the Vss of GSA did not differ between normal and cisplatin-treated rats. These results suggest that the renal elimination of GSA is attenuated in cisplatin-treated rats. In normal rats, the elimination clearance of GSA from the CSF (15.5 µL/(min·rat)) was found to be 88-fold greater than its blood-to-CSF influx clearance (0.176 µL/(min·rat)). Thus, the greater elimination clearance of GSA from the CSF, compared with the influx clearance, may contribute to the maintenance of a low GSA concentration in the CSF.
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