TY - JOUR T1 - EXCRETION OF RADIOACTIVE DIGITOXIN BY THE DOG JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 257 LP - 262 VL - 149 IS - 2 AU - B. G. Katzung AU - F. H. Meyers Y1 - 1965/08/01 UR - http://jpet.aspetjournals.org/content/149/2/257.abstract N2 - The excretion of radioactivity by dogs given single intravenous doses of tritiated digitoxin was studied, using animals with surgically prepared biliary fistulas and sham-operated dogs. Appearance of radioactivity in the bile and urine occurred within 10 minutes of administration of the digitoxin, and rate of excretion by both routes was maximal during the first 20 to 60 minutes. Sixty to 90% of the radioactivity was recovered from the aqueous phase left after chloroform extraction of these fluids, in spite of the fact that 92 to 97% of added digitoxin-T and digoxin-T could be recovered by chloroform extraction. Excretion of radioactivity in the urine of sham-operated dogs was greater and more prolonged than in fistula dogs, supporting the previously proposed enterohepatic cycle concept. The half-life of digitoxin-T in 4 dogs with total biliary fistulas averaged 6 hours, while the half-life in 4 sham-operated animals was estimated to be at least 14 hours. This difference is best explained on the basis of an enterohepatic cycle. It was found that the enterohepatic cycle hypothesis can be made more consistent with the available data by postulating the hydrolysis in the gut of water-soluble metabolites carried there in the bile, to yield digitoxin or some other relatively nonpolar glycoside. The Williams & Wilkins Comapny ER -