The Effect of Intravenous Cortisol Injections on the Plasma Cortisol Concentration in Man 1

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Abstract
Cortisol (100 mg) were injected intravenously in 5 minutes into healthy human volunteers and the concentration of steroid in plasma was followed. The rate of removal was rapid at first gradually decreasing until after 150 minutes it remained constant at a mean half-life of 138 minutes. Constant intravenous injection of cortisol (300 [mu]g/minute) caused a rising curve of concentration reaching equilibrium at 180 minutes. After the injection was stopped the concentration fell with a half-life of 124 minutes. The volume of distribution of cortisol was greater than body weight, indicating that "volume of distribution" has no real meaning. Since the steroid is concentrated in some site outside the extracellular fluid compartment, it seems likely that cortisol leaves the plasma by 2 routes: a reversible system in which the steroid is bound in high concentration to tissue proteins, and an irreversible one whereby it is permanently removed from the plasma presumably by the liver. The early part of the curve is greatly influenced by the reversible binding of steroid, whereas the later portion reflects the first-order reaction leading to irreversible destruction of the steroid.