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 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).