Effects of diammonium glycyrrhizinate on the pharmacokinetics of aconitine in rats and the potential mechanism
No Thumbnail Available
File version
Author(s)
Chen, L
Yang, J
Davey, AK
Chen, YX
Wang, JP
Liu, XQ
Yang, J
Davey, AK
Chen, YX
Wang, JP
Liu, XQ
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2009
Size
File type(s)
Location
License
Abstract
- 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.
Journal Title
Xenobiotica
Conference Title
Book Title
Edition
Volume
39
Issue
12
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject
Biochemistry and cell biology
Pharmacology and pharmaceutical sciences
Pharmacology and pharmaceutical sciences not elsewhere classified