Dose-independent pharmacokinetics of loganin in rats: effect of intestinal first-pass metabolism on bioavailability

Purpose Loganin, one of the two main iridoid glycosides in Cornus officinalis Sieb et Zucc, has been reported to exhibit many biological activities such as immune modulation, as well as anti-inflammatory and anti-shock effects. This study was designed to evaluate the pharmacokinetics of loganin, administered intravenously (5, 10, 20 and 50 mg/kg) and orally (20, 50, 100 and 200 mg/kg), in rats. Methods To evaluate its hepatic and gastrointestinal first-pass effects, loganin was administered intraportally, intragastrically and intraduodenally to rats. Results Following intravenous administration of 5-50 mg/kg loganin, a linear relationship was observed between the total area under the plasma concentration-time curve from zero to infinity (AUC) and loganin dose, with similar to 19% of the administered dose excreted in the urine. AUCs following oral administration of 20-200 mg/kg loganin were dose-independent, with the extent of absolute oral bioavailability (F) being approximately 4.87%. The AUC of loganin was significantly lower by 90.6% after intraduodenal than intraportal administration, but did not differ between intragastric and intraduodenal administration. The AUC was also significantly lower by 52.7% after intraportal, compared to intravenous, administration, suggesting that the hepatic first-pass effect on loganin after entering the portal vein was approximately 4.95% of the oral dose. Conclusion Taken together, our data suggest that the low F of loganin in rats was due exclusively to its high intestinal first-pass metabolism.