Some aspects of the biotransformation and toxicokinetic behavior of erythrosine (2',4',5',7'-tetraiodofluorescein ; FD & C Red Dye no. 3) in miniature swine

Abstract

ADD Erythrosine was orally administered to groups of four miniature pigs, Sus domesticus, for one week at daily doses of 0 (control), 2.51 and 25.2 mg/kg body weight/day. Erythrosine was absorbed into the general circulation after oral administration and appeared to increase in serum concentration after seven days in a dose-dependent manner with respect to controls. Significant increases in the total serum iodine, serum protein bound iodine and serum erythrosine iodine concentrations were observed with respect to controls. Serum thyroxine (T4), serum triiodothyronine (T3) and serum percent triiodothyronine uptake (T3 uptake) values remained unchanged from control values. Following one week oral exposure to erythrosine, the pigs were anesthetized, the jugular vein, the common bile duct and both ureters wre catheterized. Groups of pigs which had been orally exposed to 0, 2.51 and 25.2 mg/kg/day erythrosine for one week were each given the same amount (1.0 mg/kg, approximate) of erythrosine intravenously. No significant differences were noted between oral-exposure groups given erythrosine intravenously with respect to the observed changes in serum, biliary and urinary erythrosine concentrations versus time. The biliary route of erythrosine excretion was predominant over the urinary excretion route by a factor of about four. No significant induction of the hepatic drug metabolism system was observed. Whole body rectilinear scans and gamma ray camera images of the distribution of I-131 labeled erythrosine in the miniature pig after both oral and intravenous administration indicated that erythrosine was rapidly distributed to the anterior abdominal region shortly after administration via either route. Intravenously, this distribution appeared to be the result of erythrosine accumulation in the liver and kidneys. Orally, the observed distribution seemed to be attributable to the absorption of the dye from the gastrointestinal tract and subsequent accumulation of erythrosine in the liver and kidneys. The relevance of these findings to the possibility of enterohepatic cycling of erythrosine is apparent. It is concluded that further studies are required in order to more completely elucidate the complex absorption, distribution and elimination behavior of erythrosine in the miniature pig.