Combined clinical and metabolic study of the effects of alpha-methyldopa on hypertensive patients.

Abstract

The urinary metabolites of orally administered 2-14C-labeled α-methyldopa were measured in 20 hypertensive patients before and after treatment with α-methyldopa in a dose of 3.0 g daily for 3 months. There was considerable variation in the absorption, biotransformation and excretion of α-methyldopa after an oral dose, but differences in clinical response to α-methyldopa could not be attributed to this. Approximately 40% of the urinary excretion products of α-methyldopa was recovered as unchanged methyldopa, 31% as α-methyldopa-O-sulfate, 8% as 3-methoxy-α-methyldopa, 9% as neutral fraction, 3% as free base, and 3% as conjugated base. The percentage of 3-methoxy-α-methyldopa was increased following prolonged treatment with α-methyldopa, suggesting induction of catechol-O-methyl transferase. The percentage of 3-methoxy-α-methyldopa at the final study was correlated with reductions in standing blood pressure, but not with supine blood pressure. No other changes in the metabolism of α-methyldopa could be attr...