Pharmacokinetic Study of an Iridoid Glucoside: Aucubin
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Aucubin, a promising hepatoprotecting iridoid glucoside, was given intravenously (iv), orally (po), intraperitoneally (ip), and hepatoportally (pv) to rats. A linear pharmacokinetic behavior was obtained after iv administration of 40–400 mg/kg of aucubin. The half-life of aucubin in the postdistributive phase (t 1/2,β), total-body plasma clearance (CL t), and volume of distribution (Vd ss) were 42.5 min, 7.2 ml/min/kg, and 346.9 ml/kg, respectively, for a 40 mg/kg dose. There was no significant difference in the parameters as a result of increasing dose. The partition coefficients of aucubin between n-octanol and buffers of pH 3.0–10.0 were low, while 18.5 ± 1.3% of aucubin in whole blood partitioned into the blood cells. Plasma protein binding of aucubin was only 9%. The bioavailabilities of aucubin after administration at a dose of 100 mg/kg through pv, ip, and po routes were 83.5, 76.8, and 19.3%, respectively. The pH-stability profile indicated rapid degradation of aucubin at pH 1.2, 1.6, and 2.0, with degradation half-lives of 5.1, 5.8, and 14.8 hr, respectively, at 37°C. Therefore, the low oral bioavailability of aucubin may be attributed to pH-instability in the gastric fluid, poor GI absorption due to low lipophilicity, and the possible metabolism in the GI mucosa and liver (so called first-pass effect).
- R. Bernini, C. Iavarone, and C. Trogolo. 1-O-β-D-Glucopyranosyleucommiol, an iridoid glucoside from Aucuba japonica. Phytochemistry 23:1431–1433 (1984).
- A. Bianco, C. Iavarone, and C. Trogolo. Structure of eucommiol, a new cyclopentenoid-tetrol from Eucommia ulmoides. Tetrahedron 30:4117–4121 (1974).
- M. Pailer and E. Haschke-Hofmeister. Inhaltsttoffe aus Plantago major. Planta Med. 17:139–141 (1969).
- I. M. Chang and H. S. Yun. Plants with liver protective activities (II). Potential hepatotonic activities of Plantago asiatica seed. Kor. J. Pharmacog. 9:139–144 (1978).
- H. S. Yun, I. M. Chang, H. J. Choi, and S. Y. Lee. Plants with liver protective activities (IV). Chemistry and pharmacology of Plantaginis Semen et Folium. Kor. J. Pharmacog. 11:57–60 (1980).
- I. M. Chang, J. C. Ryu, Y. C. Park, H. S. Yun (Choi), and K. H. Yang. Protective activities of aucubin against carbon tetrachloride-induced liver damage in mice. Drug Chem. Toxicol. 6:443–453 (1983).
- K. H. Yang, T. J. Kwon, S. Y. Choe, H. S. Yun, and I. M. Chang. Protective effect of Aucuba japonica against carbontetrachloride-induced liver damage in rat. Drug Chem. Toxicol. 6:429–441 (1983).
- I. M. Chang, H. S. Yun, Y. S. Kim, and J. W. Ahn. Aucubin: Potential antidote for alpha-amanitin poisoning. Clin. Tox. 22:77–85 (1984).
- M. Naruto, K. Ohno, N. Naruse, and H. Takeuchi. Synthesis of prostaglandins and their congeners I. (+)-11-Deoxy-11α-hydroxymethyl prostaglandin F2α from aucubin. Tetrahedron Lett. 3:251–254 (1979).
- W. F. Berkowitz, I. Sasson, P. S. Sampathkumar, J. Hrabie, S. Choudhry, and D. Pierce. Chiral prostanoid intermediates from aucubin. Tetrahedron Lett. 19:1641–1644 (1979).
- T. Arlette, R. Yves, and G. Janine. Aucubin, a source of prostanoid synthons—new hemisynthetic pathways. Heterocycles 19:253–256 (1982).
- C. Bonini and R. D. Fabio. Assignment of correct structure to two tetrahydrodideoxy aucubins. J. Org. Chem. 47:1343–1345 (1982).
- S. Takeda, K. Yuasa, T. Endo, and M. Aburada. Pharmacological studies on iridoid compound II. J. Pharm. Dyn. 3:485–492 (1980).
- A. R. Trim and R. Hill. The preparation and properties of aucubin, asperulosides and some related glucosides. Biochem. J. 50:310–319 (1952).
- O. Sticher. The structural characterization of iridoid glucoside. In A. Sofourora (eds.), Proceedings of a Conference on African Medicinal Plants, 1979, pp. 140–168.
- I. M. Chang, Y. C. Park, and H. S. Yun (Choi). Inhibition of ribonucleic acid biosynthesis in leukemia SN36 in vitro by aucubin. Kor. Biochem. J. 15:200–204 (1982).
- A. Lenherr, B. Meier, and O. Sticher. Iridoid glucosides and acetylated flavonoids in the group of Stachys recta. Planta Med. 50:403–409 (1984).
- K. Gorier, D. Oehlke, and H. Soicke. Iridoidfuhrung von Vitex Agnus-Castus. Planta Med. 51:530–531 (1985).
- A. Franke, H. Rimpler, and D. Schneider. Iridoid glycosides in the butterfly Euphydryas cynthia (Lepidoptera, Nymphalidae). Phytochemistry 26:103–106 (1987).
- K. Yamaoka, Y. Tanigawara, T. Nakagawa, and T. Uno. A pharmacokinetic analysis program (MULTI) for microcomputer. J. Pharm. Dyn. 4:879–885 (1981).
- J. R. Gillette and K. S. Pang. Theoretical aspects of pharmacokinetic drug interactions. Clin. Pharmacol. Ther. 22:623–639 (1977).
- Y. Sugiyama. Physiological pharmacokinetics. In M. Hanano, K. Umemura, and T. Iga (eds.), Applied Pharmacokinetics—Theory and Experiments, Soft Science, Tokyo, 1985, pp. 408–409.
- P. Karrer and H. Schmid. Uber die Konstitution des Aucubins. Helv. Chim. Acta 29:525–552 (1946).
- Pharmacokinetic Study of an Iridoid Glucoside: Aucubin
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