The effect of carbenoxolone on the peripheral metabolism of cortisol in human patients.

Carbenoxolone in human patients induces a state that is similar to that seen in the syndrome of apparent mineralocorticoid excess. The mechanism in both the drug-induced and the naturally occurring disorder is thought to be the inhibition of a normal mechanism for preventing access of cortisol to the mineralocorticoid receptor, namely 11 beta-hydroxy dehydrogenation. We took the opportunity to study the effect of carbenoxolone on the peripheral metabolism of cortisol in the course of evaluating the drug's therapeutic effectiveness in pseudohypoaldosteronism. Carbenoxolone, at a dose that induces mineralocorticoid effects in patients with normally responsive mineralocorticoid receptor systems, did not lead to significant changes in the urinary cortisol: cortisone tetrahydrometabolite ratio. There was, however, a marked inhibition of ring A reduction of both cortisol and cortisone to tetrahydro metabolites. Urinary cortisol level was not significantly changed, but urinary cortisone level was decreased and the cortisol:cortisone ratio markedly increased. We conclude that the urinary cortisol:cortisone tetrahydrometabolite ratio is not necessarily a valid measure of effective inhibition of 11 beta-hydroxy dehydrogenation. A better measure of the inhibitory effect of carbenoxolone on 11 beta-hydroxy dehydrogenation is the urinary free cortisol:cortisone ratio.