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Intestinal absorption of a beta-adrenergic blocking agents nadolol. II. Mechanism of the inhibitory effect on the intestinal absorption of nadolol by sodium cholate in rats.

The mechanism of the inhibitory effect of sodium cholate and its taurine and glycine conjugates on the intestinal absorption of nadolol was investigated in rats. It was found that the uptake of nadolol into the intestinal membrane was inhibited by sodium cholate and its conjugates, but the membrane permeability to nadolol was not affected. The inhibitory effect on nadolol absorption can be interpreted in terms of loss of thermodynamic activity of nadolol due to stable micelle formation, resulting in a decrease of the uptake into the intestinal membrane. Other β-blocking agents also form micellar complexes with sodium cholate, but their micelles are ten times less stable than that of nadolol. It is concluded that the stability of the micellar complex may be an important factor in the inhibition of intestinal absorption of nadolol. The micellar stability seems to be associated with not only the chemical nature of the bile salts but also that of the drug.