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

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Abstract

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 ~ 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.

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Acknowledgements

This work was supported by a grant of the Korea Health Technology R&D Project (HR16C0001) through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare and the Basic Science Research Program (NRF-2021R1A2C1011142) through the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT), Republic of Korea.

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Authors and Affiliations

  1. College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea

    Hwi Jin Park, Sung Hun Bae & So Hee Kim

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  1. Hwi Jin Park
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  2. Sung Hun Bae
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  3. So Hee Kim
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Correspondence to So Hee Kim.

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All authors (H.J. Park, S.H. Bae, and S.H. Kim) declares that they have no conflict of interest.

Ethical approval

All experimental procedures and protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the Laboratory Animal Research Center of Ajou University Medical Center (IACUC No. 2019-0004, 2019) (Suwon, Republic of Korea).

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Park, H.J., Bae, S.H. & Kim, S.H. Dose-independent pharmacokinetics of loganin in rats: effect of intestinal first-pass metabolism on bioavailability. J. Pharm. Investig. 51, 767–776 (2021). https://doi.org/10.1007/s40005-021-00546-8

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  • DOI: https://doi.org/10.1007/s40005-021-00546-8

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