Excretion of methylproscillaridin in patients with a biliary fistula

R. Staud1, N. Rietbrock1, H. P. Fassbender1
1Dept. of Clinical Pharmacology, Klinikum Steglitz, Free University of Berlin, Federal Republic of Germany

Tóm tắt

Four patients with a biliary fistula received 0.5 mg3H-methylproscillaridin as a single oral dose. 55% of the dose was excreted in bile, 16% in urine and 3% in faeces. More than 60% of the radioactivity excreted in bile and urine appeared within the first 24 hours. 78% of the radioactivity in bile consisted of CHCl3-insoluble metabolites of methylproscillaridin, incubation of which with β-glucuronidase led to splitting off glucuronic acid from almost 80%. Methylproscillaridin can be regarded as the principal conjugated compound. TLC-separation of CHCl3-soluble compounds from bile showed identical running of radioactivity with methylproscillaridin, proscillaridin and scillarenin and three unknown metabolites P1, P2, and P3. In urine the CHCl3-soluble fraction averaged 16% to 34% of the total amount and was identified as methylproscillaridin, proscillaridin, scillarenin, P2 and P3. The relative composition of the total radioactivity in faeces amounted to 77% methyl-proscillardidin, 4% scillarenin and 12% polar metabolites.

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Tài liệu tham khảo

Abshagen, U., Rennekamp, H., Küchler, R., Rietbrock, N.: Formation and disposition of bis and monoglycosides after administration of3H-4‴ — methyldigoxin to man. Europ. J. clin. Pharmacol.7, 177–181 (1974) Belz, G.G., Belz, G., Schreiter, H.: Glykosidplasmaspiegel und Elektrokardiogramm nach einmaliger intravenöser und oraler Applikation von Methylproscillaridin bei gesunden Probanden. Verh. dtsch. Ges. inn. Med.80, 1080–1083 (1974a) Belz, G.G., Nübling, H., Schmidt-Wiederkhr, P., Franz, H.E.: Plasmakonzentration und Elimination von Methylproscillaridin bei Niereninsuffizienz. Klin. Wschr.52, 1078–1081 1974b) Greenberger, N.J., MacDermott, R.P., Martin, J.F., Dutta, S.: Intestinal absorption of six tritium labeled digitalis glycosides in rats and guinea pigs. J. Pharmacol. exp. Ther.167, 265–273 (1969) Hawksworth, G., Drasar, B.S., Hill, M.J.: Intestinal bacteria and the hydrolysis of glycosidic bonds. J. med. Microbiol.4, 451–459 (1971) Kuhlmann, J., Abshagen, U., Rietbrock, N.: Pharmacokinetics and metabolism of digoxigenin-mono-digitoxoside in man. Europ. J. clin. Pharmacol.7, 87–94 (1974) Rietbrock, N., Abshagen, U., v.Bergmann, K., Kewitz, H.: Pharmacokinetics of digoxin and its 4‴ acetyl- and methylderivates in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol.274, 171–181 (1972) Rietbrock, N., Staud, R.: Metabolism and excretion of methylproscillaridin by man. Europ. J. clin. Pharmacol.8, 427–432 (1975)