Changes in the plasma clearance and protein binding of carbenoxolone with age, and their possible relationship with adverse drug effects.

Comparison by equilibrium dialysis of plasma protein binding sites for carbenoxolone in people under 40 years of age and in people over 65 years of age showed that the number of binding sites was reduced in the elderly and that this fall was associated with a reduction in plasma albumin levels. Although carbenoxolone has some aldosterone-like effects, these properties could not be shown to be due to displacement of aldosterone from its protein binding sites by competitive protein binding of carbenoxolone. Single doses of carbenoxolone were found to be removed considerably more slowly from the plasma of elderly individuals than from the young. The results of these three series of experiments suggest that the side-effects of carbenoxolone in the elderly may in part be caused by reduced protein binding, leaving more free drug in the active unbound form, and in part by reduced hepatic clearance mechanisms.