Increases in methyldopa absorption and renal excretion after multiple doses.
A retrospective analysis of previous studies examining methyldopa absorption suggested the possibility that the absorption of methyldopa might increase on repeat methyldopa ingestion. A prospective study was undertaken to determine the effect of repeated oral doses of methyldopa on methyldopa absorption. Thirteen healthy subjects ingested single 250 mg methyldopa doses on days 0, 7, 14, 28, 56, and 112; 24 urine samples were collected and analyzed for methyldopa and its major metabolites on each study day and methyldopa plasma levels were measured over 8 hours at days 0 and 56. There were significant increases in the absorption of methyldopa (as estimated by the urinary excretion of methyldopa and the measured metabolites over 24 hours) at day 56 (33.4 +/- 8.9%, P less than .025) compared with day 0 (26.0 +/- 10.8%). There was also a significant increase in renal clearance of unmetabolized methyldopa (62.7 +/- 13.6 vs. 99.3 +/- 29.1 mL/min, P less than .01) and a decrease in the plasma half-life of methyldopa at day 56 (2.22 +/- 0.91 vs. 1.56 +/- 0.68 hr, P less than .05). There was a tendency toward increases in methyldopa absorption at day 7, 14, 28, and 112. Several possible explanations for the changes in methyldopa disposition are discussed.
Campbell
N R
NR
Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's.
Patrick
W
W
D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008750:Methyldopa / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D011446:Prospective Studies; D012189:Retrospective Studies
D008750:Methyldopa