The intestinal excretion of digitoxin in the rat.

Rats given a parenteral injection of digitoxin (1 pg. per gram of body weight) were found to excrete approximately 15 to 18 per cent of the dose in their feces. This fecal digitoxin however came from the bile, and there was no evidence of any active secretion of the glycoside by the bowel wall itself. FOR MANY YEARS workers" 2 have commented on the high degree of insensitivity to the toxic effects of the cardiac glycosides shown by rats and mice. Nevertheless , general speculation on whether this insensitivity was due to an extraordinarily effective excretion of the active cardiotonic principle or to rapid destruction of the drug within the body could not be resolved because of the limitations imposed by the quantitative tech-nics available. Recently, however, we have been able to study by means of the microsensitive embryo duck heart preparation,3 the renal role4 in the excretion of digitoxin. Here we shall complete the study of the possible excretion of this drug by communicating our findings on the intestinal excretion of cardioactive digitoxin or its aglycone. METHODS Twenty-one male adult rats of the Long-Evans strain were given digitoxin (1.0 microgram per gram of body weight) by intravenous injection. They were placed in the Bollman' type of restraining cage and the feces were collected on 17 rats the first 24 hours, on 11 during the second as well as the first 24 hour period, on eight during the third and fourth as well as the first and second days. Five additional rats were injected in the same manner after a biliary fistula had been produced in each of them. Their stools and bile were collected for 24 hours. The feces collected during any 24-hour period were dried 24 hours in vacuo at 70 C., then macerated in a Waring blender in 75 ml. of cold ethyl ether and 1.0 Gm. of diatomaceous earth for approximately two 851 minutes. This suspension was filtered and the filtrate evaporated to dryness. The residue then was taken up in Tyrode's solution, and assayed for its digitoxin content by the embryonic duck heart preparation. A standard recovery curve was prepared by adding known quantities of digitoxin to samples of rat feces (5 Gm.) and extracted precisely as outlined above for the experimental series. The presence of as little as 2 micrograms of digitoxin in a 5 Gm. sample of feces could be detected by this …