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Published:
Mar 11, 2015DOI:
10.4314/ahs.v15i1.20Keywords:
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Main Article Content
Ganoderic acid B’s influence towards the therapeutic window of trifluoperazine (TFP)
Abstract
Background: Ganoderic acid B is an important bioactive ingredient isolated from Ganoderma lucidum, and exhibits various pharmacological activities.
Aims: To investigate the influence of Ganoderic acid B towards the therapeutic window of trifluoperazine (TFP).
Methods: In vitro human liver microsomes (HLMs) incubation system was used to determine the inhibition of Ganoderic acid B towards the glucuronidation of trifluoperazine (TFP).
Results: Ganoderic acid B exerted concentration-dependent inhibition towards the glucuronidation of TFP. Furthermore, Dixon plot was used to determine the inhibition type. The intersection point was located in the second quadrant in Dixon plot, indicating the competitive inhibition of Ganoderic acid B towards TFP glucuronidation. Through fitting the data using competitive nonlinear fitting equation, the inhibition kinetic parameter was calculated to be 56.7 uM.
Conclusion: All this data indicated the potential influence of Ganoderic acid B-containing herbs towards therapeutic window of TFP. Given that the glucuronidation reaction of TFP is the probe reaction of UGT1A4, the data obtained from the present study also indicated the potential influence of Ganoderic acid-containing herbs towards the therapeutic window of drugs mainly undergoing UGT1A4-mediated metabolism.
Keywords: Ganoderic acid B, trifluoperazine (TFP), UDP-glucuronosyltransferase (UGT) 1A4
