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  • Effects of diammonium glycyrrhizinate on the pharmacokinetics of aconitine in rats and the potential mechanism

    Author(s)
    Chen, L
    Yang, J
    Davey, AK
    Chen, YX
    Wang, JP
    Liu, XQ
    Griffith University Author(s)
    Davey, Andrew
    Year published
    2009
    Metadata
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    Abstract
    1. The objective of this study was to investigate the effects of diammonium glycyrrhizinate on the pharmacokinetics of aconitine in rats and the potential mechanism. 2. After oral administration of diammonium glycyrrhizinate (50 mg kg-1), the peak plasma concentration (Cmax), area under the plasma concentration-time curve from zero to time t (AUC0-t), and absolute bioavailability of aconitine (0.2 mg kg-1) significantly increased 1.64-, 1.63- and 1.85-fold, respectively, but there was no significant change in half life (t1/2) or clearance (CL). In the other two routes of administration via the tail vein and hepatic ...
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    1. The objective of this study was to investigate the effects of diammonium glycyrrhizinate on the pharmacokinetics of aconitine in rats and the potential mechanism. 2. After oral administration of diammonium glycyrrhizinate (50 mg kg-1), the peak plasma concentration (Cmax), area under the plasma concentration-time curve from zero to time t (AUC0-t), and absolute bioavailability of aconitine (0.2 mg kg-1) significantly increased 1.64-, 1.63- and 1.85-fold, respectively, but there was no significant change in half life (t1/2) or clearance (CL). In the other two routes of administration via the tail vein and hepatic portal vein, diammonium glycyrrhizinate (15 mg kg-1) did not affect any of the pharmacokinetic parameters of aconitine (0.02 mg kg-1). Thus, diammonium glycyrrhizinate can enhance the absorption of aconitine, leading to higher oral bioavailability and plasma levels, but it does not influence its elimination. 3. Moreover, an in vitro everted gut sac model and Ussing chamber model were used to investigate the potential mechanism. Results from bidirectional transport and inhibition studies demonstrated that P-glycoprotein was the main efflux transporter involved in the absorption of aconitine in rats. The absorption enhancement effect of diammonium glycyrrhizinate should be mainly attributed to inhibiting the activity of P-glycoprotein rather than to the influence on the paracellular or transcellular transport.
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    Journal Title
    Xenobiotica
    Volume
    39
    Issue
    12
    DOI
    https://doi.org/10.3109/00498250903271997
    Subject
    Biochemistry and cell biology
    Pharmacology and pharmaceutical sciences
    Pharmacology and pharmaceutical sciences not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/37884
    Collection
    • Journal articles

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