Summary
The in vitro stability of methylproscillaridin has been compared with that of proscillaridin, the activities of the glycosides being assayed by the86Rbtechnique. After incubation in gastric juice at pH 1, 2, and 3, the activity half life of each glycoside was proportional to pH and was approximately 0.25 h, 2.5 h, and 25 h, respectively. The inactivation rate in pure hydrochloric acid at pH 2 did not differ from that in gastric juice of the same pH. The glycosides were stable in bile and enteric juice. In faeces, methylproscillaridin was stable and proscillaridin was inactivated with a half life of 32 h. It is concluded that the difference in biological availability between the two glycosides cannot be explained by differences in gastrointestinal stability.
Similar content being viewed by others
References
Andersson, K.-E., Bertler, Å., Redfors, A.: In vitro stability of proscillaridin A. Europ. J. clin. Pharmacol.8, 135–139 (1975a)
Andersson, K.-E., Bertler, Å., Redfors, A.: On the pharmacokinetics of proscillaridin A in man. Europ. J. clin. Pharmacol.8, 421–425 (1975b)
Andersson, K.-E., Bergdahl, B., Bertler, Å., Redfors, A.: On absorption of proscillaridin A after single oral doses to normal and achlorhydric subjects. Acta pharmacol. (Kbh.) In press (1976a)
Andersson, K.-E., Bergdahl, B., Dencker, H., Wettrell, G.: Proscillaridin activity in portal and peripheral venous blood after oral administration to man. Europ. J. clin. Pharmacol. In press (1976b)
Andersson, K.-E., Bergdahl, B., Wettrell, G.: Biliary excretion and enterohepatic recycling of proscillaridin A after oral administration to man. Europ. J. clin. Pharmacol. In press (1976c)
Belz, G. G.: Klinisch-experimentelle Untersuchungen mit dem Herzglykosid Proscillaridin unter besonderer Berücksichtigung seiner enteralen Resorptionsquote. Med. Klin.63, 96–102 (1968)
Belz, G. G., Stauch, M., Belz, G., Kurbjuweit, H. B., Oberdorf, A.: The effect of various cardenolides and bufadienolides with different cardiac activity on the86Rb-uptake of human erythrocytes. Naunyn-Schmiedeberg's Arch. Pharmacol.280, 353–363 (1973)
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 (1974)
Belz, G. G., Nübling, H., Belz, G.: Plasma concentrations during repeated intravenous and oral methyl-proscillaridin application in man. Arzneimittel-Forsch.26, 277–278 (1976)
Bertler, Å., Redfors, A.: An improved method of estimating digoxin in human plasma. Clin. Pharmacol. Ther.11, 665–673 (1970)
Brücke, F.: Über die Zerstörbarkeit herzwirksamer Glykoside durch Säure und Alkali. Naunyn-Schmiedeberg's Arch. Pharmak. exp. Path.182, 444–451 (1936)
Butzengeiger, K. H., Graeber, U., Lange, J., Schumacher, R.: Therapeutische Prüfung von Proscillaridin A. Dtsch. med. Wschr.92, 2212–2214, 2217 (1967)
Hänel, J., Meiffert, G.: Klinisch-experimentelle Studie zur Charakterisierung eines Herzglykosids. Med. Welt.17, 1404–1408 (1966)
James, A. H., Pickering, G. W.: The role of gastric acidity in the pathogenesis of peptic ulcer. Clin. Sci.8, 181–210 (1949)
Kasahara, K., Ruiz-Torres, A.: Einwirkung der Verdauungssäfte auf die Beständigkeit des Digoxin- und Digitoxin-Moleküls. Klin. Wschr.47, 1109–1111 (1969)
Kaufman, J. M., Belpaire, F. M.: The influence of metabolites of digoxin and digitoxin on the86Rb-uptake assay. Europ. J. clin. Pharmacol.6, 54–56 (1973)
Krämer, K.-D., Hochrein, H.: Enterale Verfügbarkeit und therapeutische Wirksamkeit von Proscillaridin-4′-methyläther. Arzneimittel-Forsch.26, 579–583 (1976)
Kuhlmann, J., Abshagen, K., Rietbrock, N.: Cleavage of glycosidic bonds of digoxin and derivatives as function of pH and time. Naunyn-Schmiedeberg's Arch. Pharmak. exp. Path.276, 149–156 (1973)
Lennard-Jones, J. E., Fletcher, J., Shaw, D. G.: Effect of different foods on the acidity of the gastric contents in patients with duodenal ulcer. Part III: Effect of altering the proportions of protein and carbohydrate. Gut9, 177–182 (1968)
Löschhorn, N.: Probleme der quantitativen Prüfung von Herzglykosiden, dargestellt an Proscillaridin. Therapiewoche19, 1529–1532 (1969)
Meier, G., Wagner, G.: Therapeutische Erfahrungen mit einem neuen Herzglykosid: Proscillaridin A. Med. Welt18, 1995–2002 (1965)
Staud, R., Rietbrock, N., Fassbender, H. P.: Excretion of methylproscillaridin in patients with a biliary fistula. Europ. J. clin. Pharmacol.9, 99–103 (1975)
Švec, F.: Zerstörbarkeit der Digitalissubstanzen im Magensaft. Naunyn-Schmiedeberg's Arch. Pharmak. exp. Path.185, 57–70 (1937)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bergdahl, B., Andersson, K.E. Stability in vitro of methylproscillaridin. Eur J Clin Pharmacol 11, 267–271 (1977). https://doi.org/10.1007/BF00607675
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00607675