CLINICAL PHARMACOLOGY
CORTROSYN™ (cosyntropin) for Injection exhibits the full corticosteroidogenic activity of natural ACTH. Various studies have shown that the biologic activity of ACTH resides in the N-terminal portion of the molecule and that the 1 – 20 amino acid residue is the minimal sequence retaining full activity. Partial or complete loss of activity is noted with progressive shortening of the chain beyond 20 amino acid residues. For example, the decrement from 20 to 19 results in a 70% loss of potency.
The pharmacologic profile of CORTROSYN™ is similar to that of purified natural ACTH. It has been established that 0.25 mg of CORTROSYN™ will stimulate the adrenal cortex maximally and to the same extent as 25 units of natural ACTH. This dose of CORTROSYN™ will produce maximal secretion of 17-OH corticosteroids, 17- ketosteroids and / or 17 - ketogenic steroids.
The extra-adrenal effects which natural ACTH and CORTROSYN™ have in common include increased melanotropic activity, increased growth hormone secretion and an adipokinetic effect. These are considered to be without physiological or clinical significance.
Animal, human and synthetic ACTH (1–39) which all contain 39 amino acids exhibit similar immunologic activity. This activity resides in the C-terminal portion of the molecule and the 22–39 amino acid residues exhibit the greatest degree of antigenicity. In contrast, synthetic polypeptides containing 1–19 or fewer amino acids have no detectable immunologic activity. Those containing 1–26, 1–24 or 1–23 amino acids have very little immunologic although full biologic activity. This property of CORTROSYN™ assumes added importance in view of the known antigenicity of natural ACTH.
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