The effect of pH and concentration on α-methyldopa absorption in man

Abstract

An open crossover study of the absorption of α-methyldopa has been conducted in normal healthy adult male volunteers in whom a triple lumen perfusion tube had been placed. Three volunteers were perfused on separate occasions with 0.1 mM α-methyldopa at pH 4.5, 6.0 and 7.4. Three other volunteers were perfused on separate occasions with 0.1, 1.0 and 10 mM α-methyldopa at pH 6.0. Two additional subjects were perfused with 0.1 mM α-methyldopa at pH 6.0. Absorption was not a linear function of concentration above 1 mM α-methyldopa. There was also a weak trend toward greater absorption near pH 6.0. At higher concentrations of drug in the perfusion solution (10 vs 1 mM), the free fraction of α-methyldopa in plasma samples was increased significantly. Thus, although absorption of α-methyldopa is more efficient at lower concentrations, bioavailability may not be substantially enhanced due to increased sulphation in the gut wall. Comparison of permeabilities with previous results from our laboratories suggests the rat is a good model for predicting the behaviour of α-methyldopa after its oral administration to man.