Campbell N R, Patrick W
Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's.
J Clin Pharmacol. 1992 May;32(5):450-4. doi: 10.1002/j.1552-4604.1992.tb03861.x.
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.
一项对既往研究甲基多巴吸收情况的回顾性分析表明，重复摄入甲基多巴可能会增加其吸收。为此开展了一项前瞻性研究，以确定重复口服甲基多巴剂量对甲基多巴吸收的影响。13名健康受试者在第0、7、14、28、56和112天分别单次服用250毫克甲基多巴；在每个研究日收集24份尿液样本，分析其中甲基多巴及其主要代谢产物，并在第0天和第56天测量8小时内的甲基多巴血浆水平。与第0天（26.0±10.8%）相比，第56天甲基多巴的吸收显著增加（以24小时内甲基多巴的尿排泄量和所测代谢产物估算，为33.4±8.9%，P＜0.025）。未代谢甲基多巴的肾清除率也显著增加（62.7±13.6对99.3±29.1毫升/分钟，P＜0.01），且第56天甲基多巴的血浆半衰期缩短（2.22±0.91对1.56±0.68小时，P＜0.05）。在第7、14、28和112天，甲基多巴的吸收有增加趋势。文中讨论了甲基多巴处置变化的几种可能解释。
