Pharmacokinetics of methyldopa in renal failure and bilaterally nephrectomized patients.

The elimination from plasma of 14C-labelled methyldopa was studied in three bilaterally nephrectomized patients and four patients with reduced renal function. The elimination of radioactivity was slow, particularly in the anephric patients where about 50% of the injected dose was still present in plasma after 48 hours. Chemically determined methyldopa disappeared from plasma much faster than radioactivity in both groups of patients, suggesting formation and retention of metabolite(s). The urinary excretion rate of both radioactivity and unchanged drug in the patients with renal failure was slow in comparison with normal subjects. Moreover, the composition of the 0–48 hour urine differed from that of normals, showing a lowered content of unchanged drug. Slow elimination of unidentified metabolite(s) might possibly explain the strong and prolonged hypotensive action of methyldopa in patients with renal failure.