Effect of dose and route of administration of ACTH 1–24 on plasma Cortisol concentrations in ewes

Doses of 0.005-1.0 mg of ACTH1-24 given intravenously, intramuscularly or as an intramuscular depot injection caused increases in cortisol concentrations within 15 min in the plasma of ewes. There was, however, considerable animal-to-animal variation in maximum concentrations achieved. A curvilinear dose-response relationship to ACTH1-24 was obtained which was similar for each route of administration when expressed in terms of maximum cortisol concentrations. However, for a given dose, more prolonged release of cortisol occurred after i.m. injection compared to i.v., with maximum concentrations occurring 6 h after the depot formulation injection. Five repeated daily doses of 1.0 mg depot ACTH1-24 resulted in no diminution of cortisol response indicating considerable synthesizing capacity of the adrenals in clinically normal ewes. Comparison of cortisol concentrations after an acute stressor (shearing) suggests that doses of ACTH1-24 greater than 0.25 mg are excessive for simulation of stress-induced adrenal activity.