Species difference in the inhibitory potentials of non-steroidal anti-inflammatory drugs on the hepatic sulfation and glucuronidation of bioactive flavonoids: differential observations among common inhibition parameters

Abstract

1. This study elucidated the species differences between rats and humans in the inhibitory potential of drugs against sulfation and glucuronidation, and whether such differences depend on the inhibition parameter adopted.

2. With 14 non-steroidal anti-inflammatory drugs (NSAIDs) as model inhibitors and three flavanoids baicalein, wogonin and oroxylin A as model substrates, three common inhibition parameters percentage of control, IC₅₀ and K_i were determined in rat liver cytosols (RLCs), human liver cytosols (HLCs), rat liver microsomes (RLMs) and human liver microsomes (HLMs). The closeness of the inhibition parameters from rat liver preparations to that from human liver preparations was analyzed by geometric mean fold error (GMFE) and statistical comparisons.

3. The percentage of control in RLC/RLM was not significantly different from that in HLC/HLM, with a GMFE of 0.85 (RLC–HLC) and 1.03 (RLM–HLM); whereas the IC₅₀ and K_i in RLC/RLM were significantly different from that in HLC/HLM. The trend of difference was consistent between IC₅₀ and K_i, where these parameters in RLC and RLM underestimated (GMFE <0.5) and overestimated (GMFE >2) that in HLC and HLM, respectively.

4. In conclusion, the inhibitory potentials of NSAIDs against sulfation and glucuronidation in rats and humans were different and depended on the adopted inhibition parameters.

• Human
• liver cytosols
• liver microsomes
• rat
• SULT
• UGT

Notice of Correction:

In the version of this article published online ahead of print on 30 October 2013 the declaration of interest was incomplete. The following information was omitted: “This work was supported by the Research Grants Council, Hong Kong SAR [CUHK480010].” The error has been corrected for this version.