DIAGNOSTIC STUDY OF A SYNTHETIC HUMAN CORTICOTROPIN-RELEASING HORMONE (HCRH) IN HEALTHY ADULT MALES - ITS PLASMA PHARMACOKINETICS AND THE EFFECTS ON THE URINARY-EXCRETION OF STEROID-HORMONES

The pharmacokinetics, responses of plasma ACTH and cortisol, urinary excretion of steroid hormones, and safety of MCI-028, a synthetic human corticotropin-releasing hormone (hCRH), were examined in eight healthy adult male volunteers after intravenous administration of 33, 100 and 200 mu g of the drug. The disappearance of MCI-028 from plasma could be fitted to a biexponential decay curve, the plasma half-lives (T-1/2) were 0.12 to 0.15 h for alpha phase, and 0.57 to 0.67 h for beta phase. Plasma ACTH and cortisol concentrations and the urinary excretion of steroid hormones (particularly free cortisol) increased significantly in relation to the MCI-028 dose administrated. Although hot flushing and an increase in the heart rate were observed at higher doses, they were mild and transient. It is also considered that the urinary excretion of free cortisol after the administration of MCI-028 can be an index reflecting the functioning of this system.