Metabolic disposition and cardiovascular effects of methyldopate in unanesthetized rhesus monkeys

Methyldopate, the ethyl ester hydrochloride salt of alpha-methyldopa (alpha-MD), is used extensively in the treatment of severe hypertension. We have developed a high-pressure liquid chromatographic assay to determine the plasma-time concentrations of alpha-MD after intravenous administration of methyldopate and alpha-MD in the monkey in an effort to evaluate the bioavailability of alpha-MD and the extent of in vivo hydrolysis of the amino ester to the amino acid. The results establish that in this experimental situation methyldopate is not metabolically equivalent to alpha-MD.