Summary
14C-labelled lisuride hydrogen maleate was administered intravenously (25 ug) and orally (200 ug) 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 1 4C-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 halflife 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 atC2/C3 and C9/Ci0.
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Hümpel, M., Krause, W., Hoyer, G.A. et al. The pharmacokinetics and biotransformation of14C-Lisuride hydrogen maleate in rhesus monkey and in man. European Journal of Drug Metabolism and Pharmacokinetics 9, 347–357 (1984). https://doi.org/10.1007/BF03189685
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DOI: https://doi.org/10.1007/BF03189685