The metabolism of14C-labelled α-methyldopa in normal and hypertensive human subjects

Abstract

1. The fate of orally administered14C-labelled l-α-methyldopa has been examined in three normal men and in eight hypertensive patients who responded to the drug and three who did not. 2. The output of14C in the urine in 2 days and in the faeces in 4 days was not very different in any of the subjects. The normals excreted about 40% of the dose in the urine and 60% in the faeces, the responders 52% (range 35–60%) and 45% and the non-responders 42% and 41%. Most of the urinary14C radioactivity was eliminated in 24h after dosing. 3. The main metabolite in the urine was free and conjugated α-methyldopa (normal men, 23% responders, 37% non-responders, 25% of the dose). Free and conjugated 3-O-methyl-α-methyldopa was about 4% in all subjects, total amines (α-methyldopamine and 3-O-methyl-α-methyldopamine) about 6% and ketones (mainly 3,4-dihydroxyphenylacetone) about 3%. 4. The output of α-methyldopamine (2–4% of dose), 3-O-methyl-α-methyldopamine (0.3%) and 3,4-dihydroxyphenylacetone (3–5%) was similar in the one normal and two responders examined. 5. The faecal14C in all subjects was unchanged l-α-methyldopa. 6. In general, the amounts of the metabolites in the urine in normal men and in responding and non-responding patients were quantitatively similar, except in one non-responding patient who converted nearly two-thirds of the absorbed drug into amines and ketones. There appeared to be no correlation between metabolites in the urine and response or lack of response to the drug. 7. In two normal subjects 70–80% of d-α-methyldopa was excreted unchanged in the faeces. Of the absorbed compound most (9–14% of the dose) was excreted as the free and conjugated drug together with a small amount (1–2%) of 3-O-methyl-α-methyldopa. No amines and only traces of ketone were excreted.