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Pharmacokinetic study of an iridoid glucoside: aucubin.

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 administation of 400-400 mg/kg of aucubin. The half-life of aucubin in the postdistributive phase (t1/2, beta), total-body plasma clearance (CLt), and volume of distribution (Vdss) 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 reult 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 bioavailabilites 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 degrees 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).[1]

References

  1. Pharmacokinetic study of an iridoid glucoside: aucubin. Suh, N.J., Shim, C.K., Lee, M.H., Kim, S.K., Chang, I.M. Pharm. Res. (1991) [Pubmed]
 
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