Hümpel M, Krause W, Hoyer G A, Wendt H, Pommerenke G
Eur J Drug Metab Pharmacokinet. 1984 Oct-Dec;9(4):347-57. doi: 10.1007/BF03189685.
14C-labelled lisuride hydrogen maleate was administered intravenously (25 micrograms) and orally (200 micrograms) to three male and three female elderly volunteers. Following i.v. injection radioimmunologically determined plasma levels of unchanged lisuride showed a three-phasic decline with half-lives of 3 minutes, 16 minutes and 2.9 hours. The total clearance was 16 +/- 9 ml/min/kg. Bioavailability was estimated to be 14% of oral dose. Determination of 14C-radioactivity did not show any specific enrichment of lisuride metabolites in cellular components of blood. The drug was almost totally metabolized and its degradation products were eliminated equally via the kidney and liver. Total recovery was about 90% of dose. The elimination half-life was 10 hours. Small parts of the dose administered were renally excreted with a half-life of 23 hours. Lisuride is metabolized extensively. HPLC radiochromatograms of freely extractable metabolites from urine did not show marked differences between both routes of administration. More than 15 compounds were freely extractable, only one of them represented more than 5% of dose. Phase II reactions were quantitatively unimportant. From rhesus monkey urine 6 metabolites were isolated. Chemical structures were proposed for 5 of them. They were assigned to the pattern of freely extractable human urinary metabolites and covered about 50% of radiolabel corresponding to about 13% of dose. The main freely extractable urinary metabolite was thought to be the 2-keto-3-hydroxy-lisuride derivative. Structures of the other four metabolites and earlier observations on the stability of the N'-ethyl-3H label led to the interpretation of independent changes of lisuride by different enzymatic processes such as oxidative N-deethylation, hydroxylation of the benzene system, monooxygenation at C2 and C9, and oxidation of double bonds at C2/C3 and C9/C10.
给三名老年男性和三名老年女性志愿者静脉注射（25微克）和口服（200微克）14C标记的马来酸麦角乙脲。静脉注射后，放射免疫法测定的未代谢麦角乙脲血浆水平呈三相下降，半衰期分别为3分钟、16分钟和2.9小时。总清除率为16±9毫升/分钟/千克。生物利用度估计为口服剂量的14%。对14C放射性的测定未显示麦角乙脲代谢物在血液细胞成分中有任何特异性富集。该药物几乎完全代谢，其降解产物通过肾脏和肝脏等量消除。总回收率约为剂量的90%。消除半衰期为10小时。给药剂量的一小部分经肾脏排泄，半衰期为23小时。麦角乙脲代谢广泛。尿液中可自由提取的代谢物的高效液相色谱放射色谱图在两种给药途径之间未显示明显差异。有超过15种化合物可自由提取，其中只有一种占剂量的5%以上。第二相反应在数量上不重要。从恒河猴尿液中分离出6种代谢物。为其中5种提出了化学结构。它们被归入可自由提取的人尿代谢物模式，涵盖约50%的放射性标记，相当于约13%的剂量。主要的可自由提取的尿代谢物被认为是2-酮-3-羟基麦角乙脲衍生物。其他四种代谢物的结构以及对N'-乙基-3H标记稳定性的早期观察结果导致通过不同的酶促过程对麦角乙脲的独立变化进行解释，如氧化N-去乙基化、苯环羟基化、C2和C9处的单加氧作用以及C2/C3和C9/C10处双键的氧化。
