Kinetics of plasma homocysteine in healthy subjects after peroral homocysteine loading

Abstract

The kinetics of plasma homocysteine were determined in 13 healthy subjects after peroral administration and in one person after intravenous injection. Various forms of homocysteine completely dissolved in an aqueous solution were rapidly absorbed after peroral administration, and the bioavailability was estimated to be 0.53. The volume of distribution was 0.66 L/kg. The area under the plasma concentration curve (AUC0-48 h) was proportional to the administered dose (33.5-134 μmol/kg body wt), and showed small interindividual variations. Plasma homocysteine showed first-order elimination kinetics for at least 6 h. The half-life (t1/2) was 223 ± 45 min, and there was a significant correlation between t1/2 values determined on two different occasions in the same individual. The transient hyperhomocysteinemia was associated with an increase in plasma methionine, which probably reflects intracellular remethylation of homocysteine. Less than 2% of the administered homocysteine dose was recovered in the urine. These findings may form the basis for future studies on the regulation of plasma homocysteine in health and disease, and should motivate the evaluation of a homocysteine loading test as a diagnostic tool.