Summary
The plasma level profile and the biliary excretion of silybin, the main flavanolignan component of silymarin, were evaluated in rats after single equimolar oral doses (200 mg/kg, expressed as silybin equivalents) of the silybin-phosphatidylcholine complex silipide (laboratory code IdB 1016) and of silymarin. Silybin was assayed by using a specific HPLC method which allowed also the determination of other flavanolignans present in the biological fluids after administration of silymarin (i.e. silydianin, silycristin and isosilybin).
After oral silipide, silybin reached peak plasma levels within 2 h, with a Cmax of 9.0±3.0 μg/ml for unconjugated drug and 93.4±16.7 μg/ml for total (free + unconjugated drug). Maximum total biliary concentrations of silybin (2989±568 μg/ml) were observed within 2 h and the biliary recovery after 24 h accounted for about 13% of the administered amount.
After administration of silymarin, unconjugated and total plasma silybin levels as well as biliary excretion were several-fold lower than those observed after treatment with silipide. Silybin recovered over a 24 h period after silymarin intake accounted for about 2% of the administered dose.
Plasma and bile obtained after administration of silymarin contained also silydianin, silycristin and, to a greater extent, isosilybin. The concentrations of the latter compound in plasma and in bile were higher than those of silybin itself.
The relative bioavailability of silipide (calculated in the target organ as the ratio between AUCs of cumulative biliary excretion curves) was 10-fold higher than that of silymarin.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hruby K., Cosmos G., Fuhrmann M., Thaler H. (1983): Chemotherapy ofAmanita phalloides poisoning with intravenous silibinin. Human Toxicol. 2, 183–195.
Ferenci P., Dragosics B., Frank H., Benda L., Dittrich H., Meryn S. (1985): Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J. Hepatol., 1, S229.
Ferenci P., Dragosics B., Dittrich H., et al. (1989): Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J. Hepatol., 9, 105–113.
Morazzoni P., Magistretti M.J., Giachetti C., Zanolo G. (1992): Comparative bioavailability of silipide, a new flavanolignan complex, in rats. Eur. J. Drug Metab. Pharmacokinet, 17, 39–44.
Arcari M., Brambilla A., Brandt A., et al. (1992): Nuovo complesso di inclusione tra la silibina e la β-ciclodestrina: velocità di dissoluzione in vitro e assorbimento in vivo in confronto a formulazioni tradizionali. Boll. Chim. Farmaceutico, 131, 205–209.
Zanolo G. (1989): RBM Exp. n. 254, Invemi della Beffa SpA, data on file.
Livio S., Seghizzi R., Pifferi G. (1990): Diffusion behaviour of IdB 1016, across artificial and biological membranes. 4th European Congress of Biopharmaceutics and Pharmacokinetics, Geneva, 17–19 April.
Gabetta B., Zini G.F., Pifferi G. (1989): Spectroscopic studies on IdB 1016, a new flavanolignan complex. Planta Medica, 55, 615.
Conti M., Malandrino S., Magistretti M.J. (1992): Protective activity of silipide on liver damage in rodents. Jpn J. Pharmacol., 60, 315–321.
Morazzoni P., Malandrino S., Pifferi G. (1992): Comparative bioavailability of a silybin-phosphatidylcholine complex and silymarin in rats. In: Brès J., Panis G. (eds). Pharmacocinétique: de la recherche à la clinique. John Libbey Eurotext, pp. 363–364.
Barzaghi N., Crema F., Gatti G., Pifferi G., Perucca E. (1990): Pharmacokinetic studies on IdB 1016, a silybin-phosphatidylcholine complex, in healthy human subjects. Eur. J. Drug Metab. Pharmacokinet., 15, 333–338.
Orlando R., Fragasso A., Lampertico M., Marena C. (1990): Silybin kinetics in patients with liver cirrhosis: a comparative study of a silybin-phosphatidylcholine complex and silymarin. Med. Sci. Res. 18, 861–863.
Schandalik R., Gatti G., Perucca E. (1992): Pharmacokinetics in bile following administration of silipide and silymarin in cholecystectomy patients. Arzneimittelforsch., 42(II), 964–968.
Martinelli E.M., Morazzoni P., Livio S., Uberti E. (1991): Liquid chromatographic assay of silybin in human plasma and urine. J. Liq. Chromatogr., 14, 1285–1296.
Bülles H., Bülles J., Krumbiegel G., Mennicke W.H., Nitz D. (1975): Untersuchungen zur Verstoffwechselung und zur Ausscheidung von Silybin bei der Ratte. Arzneimittelforsch., 25, 902–905.
Lambert R. (1965): Surgery of the bile duct. In: Thomas C. (ed). Surgery of the Digestive System in the rat. Springfield, Illinois, USA.
Mennicke W.H. (1975): Zur biologischen Verfügbarkeit und Verstoffwechselung von Silybin. Dtsch. Ap. Ztg., 115, 1205–1206.
Comoglio A., Leonarduzzi G., Carini R., et al. (1990): Studies on the antioxidant and free radical scavenging properties of IdB 1016 a new flavanolignan complex. Free Rad. Res. Commun., 11, 109–115.
Meyer-Burg J. (1972): Zur Frage der Resorption von Silymarin bei der Ratte. Klin. Wschr., 50, 1060–1061.
Flory P.J., Krug G., Lorenz D., Mennicke W.H. (1980): Untersuchungen zur Elimination von Silymarin bei cholezystektomierten Patienten. Planta Medica, 38, 227–237.
Ognyanova W., Drenska A., Mikhailova D., Nachev I. (1981): Pharmacokinetics of Carsil (silymarin) in experimental animals. Eksp. Med. Morfol., 19, 214–220.
Lorenz D., Lücker P.W., Mennicke W.H., Wetzelsberger N. (1984): Pharmacokinetic studies with silymarin in human serum and bile. Meth. Find. Exp. Clin. Pharmacol. 6, 655–661.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Morazzoni, P., Montalbetti, A., Malandrino, S. et al. Comparative pharmacokinetics of silipide and silymarin in rats. Eur. J. Drug Metab. Pharmacokinet. 18, 289–297 (1993). https://doi.org/10.1007/BF03188811
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03188811