Sulfate and methyldopa metabolism: Metabolite patterns and platelet phenol sulfotransferase activity

Sulfate conjugation catalyzed by phenol sulfotransferase (PST) is the major metabolic pathway for methyldopa. Methyldopa is also O-methylated in a reaction catalyzed by catechol-O-methyltransferase (COMT). Our studies were performed to determine whether sodium sulfate alters methyldopa metabolism. Methyldopa powder, 3.5 mg/kg, was taken with and without sodium sulfate, 13.25 mg/kg, by 24 subjects in a randomized, crossover design. Compared with results obtained when only methyldopa was taken, sodium sulfate taken with methyldopa increased the proportion of drug excreted as methyldopa sulfate expressed as the percentage of all urinary metabolites (66.0% ± 5.3% and 50.1% ± 7.5%; X ± SD). The percentage of free methyldopa excreted also decreased (17.1% ± 3.7% and 27.3% ± 5.5%). Platelet PST and red blood cell COMT activities were measured in blood samples from these subjects. When sodium sulfate was taken with methyldopa, there was a significant correlation between platelet PST activities and percentages of metabolites excreted as methyldopa sulfate (r = 0.545; P < 0.01). This correlation was not significant when methyldopa was taken alone (r = -0.340; P > 0.10). There was a significant correlation between red blood cell COMT activities and the proportion of urinary metabolites excreted as 3-O-methyl-α-methyldopa when methyldopa was taken alone (r = 0.532; P < 0.01) but not when it was taken with sodium sulfate (r = 0.153; P > 0.20). Our data support the conclusion that variation in sulfate availability may be one factor responsible for individual differences in the metabolism of clinically used doses of methyldopa. Platelet PST activity correlates with individual variations in the sulfate conjugation of methyldopa taken by mouth with sodium sulfate.