Conjugation of Methyldopa in Renal Failure

Abstract

During oral treatment with methyldopa an accumulation in plasma of its main metabolite, methyldopa-O-sulphate, was observed. Therefore, the rate of drug conjugation was studied after intravenous injection of methyldopa in 4 patients with advanced renal insufficiency and 4 patients with essential hypertension without impaired renal function. The rate of conjugation of methyldopa was decreased in renal insufficiency compared with patients with essential hypertension and normal kidney function. The present study strongly suggests that the accumulation of methyldopa-O-sulphate was due to decreased elimination in renal insufficiency. Increased sensitivity to the hypotensive effect of methyldopa in renal failure was not due to increased plasma levels of the unconjugated drug, but to accumulation of methyldopa-O-sulphate.

Key Words:

• Methyldopa
• pharmacokinetics
• renal failure