Therapeutic Window Alteration of Irinotecan by Ginsenosides

The toxicity of irinotecan has been mainly induced by its active metabolite SN-38, and the inhibition of the glucuronidation process of SN-38 can significantly increase the toxicity of irinotecan. The present study aims to evaluate the inhibition of SN-38 glucuronidation by ginsenoside C-K, trying to indicate the influence of the administration of ginsenosides or ginseng towards the therapeutic window and toxicity of irinotecan. In vitro incubation system was used to determine the inhibition of ginsenoside C-K towards the glucuronidation of SN-38 catalyzed by two different enzyme sources: recombinant UGT1A1 and human liver microsomes (HLMs). The results showed ginsenoside C-K exhibited noncompetitive inhibition towards recombinant UGT1A1-mediated glucuronidation of SN-38, and competitive inhibition towards HLMs-catalyzed glucuronidation of SN-38. The obtained inhibition kinetic parameters can be employed to extrapolate in vivo inhibition magnitude when the in vivo concentration will be clarified in the future.