An open crossover study of the absorption of alpha-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 alpha-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 alpha-methyldopa at pH 6.0. Two additional subjects were perfused with 0.1 mM alpha-methyldopa at pH 6.0. Absorption was not a linear function of concentration above 1 mM alpha-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 alpha-methyldopa in plasma samples was increased significantly. Thus, although absorption of alpha-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 alpha-methyldopa after its oral administration to man.

The intestinal absorption of alpha-methyldopa from perfused segments of rat intestine was determined. Jejunal and ileal segments were studied at pH 4.5, 6.0 and 7.4 at an alpha-methyldopa concentration of 0.01 mM, and at pH 6.0 at concentrations of 0.01, 0.10 and 10 mM. Intestinal absorption was found to depend on both concentration and pH but not on segment. A weak positive correlation (r = 0.5) was observed between net water absorption and alpha-methyldopa absorption, similar to that observed for amino acids. The low intestinal wall permeability of alpha-methyldopa under normal intestinal pH conditions (pH 7.4) is consistent with the incomplete oral bioavailability of this drug.

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