HEPATIC UPTAKE AND BILIARY-EXCRETION OF A BILE-SALT ANALOG - GLYCODIHYDROFUSIDATE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 26 (1), 60-64
Abstract
Glyco-24,25-dihydrofusidate is efficiently excreted in the bile by the liver. This compound partially inhibits hepatobiliary transport of bile salts and bilirubin. In order to determine if bile salts and glycodihydrofusidate share common pathways at the hepatocyte level, the effect of sodium dehydrocholate on the blood clearance of glycodihydrofusidate was studied. Two groups of rats were perfused, controls with 0.15 M NaCl, and test animals with 10 .mu.mol .times. min-1 .times. kg-1 of dehydrocholate; both groups received 1 .mu.Ci of 14C-glycodihydrofusidate i.v. Carotid blood was removed every minute and the disappearance of radioactivity from the blood was monitored. The results are consistent with a theoretical model of 2 compartments. The experimental curves were fed to the sum of exponentials. The fractional transfer rate (blood towards liver) of glycodihydrofusidate is significantly (2 P < 0.05) higher in control rats (k21 = 1.091 .+-. 0.030) min-1) than in dehydrocholate-treated animals (k21 = 0.585 .+-. 0.056 min-1). The fractional transfer rate (liver towards bile) is: k02 = 0.083 .+-. 0.007 min-1 for control animals and is significantly reduced (2 P < 0.05) in the presence of dehydrocholate (k02 = 0.030 .+-. 0.003 min-1). The uptake and biliary excretion of glycodihydrofusidate involves, at least partially, the transport mechanisms employed for bile salts.