METHODS OF ADMINISTERING DESOXYCORTICOSTERONE AND THE PROBLEM OF ITS INACTIVATION BY THE LIVER1

Abstract

To test the role of the liver in the inactivation of desoxycorticosterone acetate (DCA) 1 or 3 desoxycorticosterone acetate-cholesterol pellets, averaging 2.27 mg. each and consisting of 2/3 cholesterol, were implanted into 120 young adrenalectomized rats to sites presumably a) with portal drainage (spleen, mesentery, caecal lymph gland), b) without portal drainage (subcutaneous, renal, cervical lymph gland). For another series of 18 animals, DCA was mixed with the food and administered to each animal in a daily dose of 0.2 mg. for comparison with the effectiveness of a similar dose injected subcutaneously into 11 animals. Sixty adrenalectomized rats served as controls. All pellets, wherever placed, were effective in maintaining adrenalectomized rats. Their effectiveness, however, was reduced when absorption occurred from pellets having portal drainage, probably indicating partial inacti-vation by the liver. Three pellets were more effective than 1, but only 44% of the animals with 3 pellets survived more than 30 days and the avg. growth rate was about 1/2 that of normal rats. In contrast, 70% of the animals with 3 pellets at sites without portal drainage survived more than 30 days and the growth rate approached normal. DCA was about 1/2 as effective when given as a mixture in the dry food than when administered parenterally, indicating a partial inacti-vation by the liver when absorption takes place from the gut.