Beitrag zur Verteilung und Wirkung des Colchicins im Tierkörper

Abstract
Since colchicine interferes with mitosis, it has been suggested as a therapeutic agent in the treatment of tumors. Colchicine is very toxic and is usually administered to small laboratory animals in doses of about 100-300 [gamma]. To detn. colchicine in the tissues of the animal after admn., the organ is ground with several times its wt. of anhydrous Na2SO4, the mixture covered with chloroform and allowed to stand 24 hrs. The mixture is filtered, the chloroform extract evaporated and the residue extracted with hot sterile Ringer soln. The mitosis-poisoning action of the extract is tested on chicken heart fibroblasts. As little as 0.06 [gamma] colchicine/ml. extract is detected. A guinea pig 250 g. in wt. is injected with 250 [gamma] colchicine intraperitoneally and dies after 9 hrs. The great-est amt. of the colchicine is recovered in the liver, bile, and intestine, the organs by which the drug is mostly excreted. The drug is also present in the blood, kidneys and lungs, but not in the brain. Some of the colchicine is excreted by the kidneys and by the stomach mucosa. In mice injected intraperitoneally with 105 [gamma] colchicine and killed after 16 hrs., all of the compound has disappeared from the liver, but some is still present in the intestine. In mice injected with 30-120 [gamma] colchicine, it is shown that the injected dose must be at least 45 [gamma] in order to detect the drug in the liver after 5 hrs. Dormant mice kept in the cold tolerate more of the drug than young growing mice. Since the drug is active as a mitosis poison in the presence of vit. C, it does not have to undergo an oxidative change in order to achieve its toxic action. Treatment with the thyrotrophic hormone increases the sensitivity of guinea pigs towards the drug. The local application of colchicine and its derivatives seems to inhibit the growth of external tumors.