20(S)-Protopanaxatriol (Ppt) Exhibits Inhibition Towards UDP-Glucuronosyltransferase (UGT)-Catalyzed Zidovudine Glucuronidation

Drug-drug interaction (DDI) is a challenging problem for treatment of HIV-infected patients. Zidovudine (AZT), prescribed under the names Retrovir and Retrovis, is the first U.S. government-approved antiretroviral drug used for the successful treatment of HIV/AIDS infectiousness. Given that ginseng is frequently utilized in combination with AZT and AZT is mainly eliminated by UDP-glucuronosyltransferase 2B7, the aim of present study is to investigate the inhibition of UGT2B7-catalyzed AZT glucuronidation by 20(S)-protopanaxatriol type (Ppt) which is the main ginsenoside absorbed into the plasma. The results showed that ppt competitively inhibited UGT2B7-catalyzed AZT glucuronidation, and the inhibition kinetic parameter (K-i) was determined to be 24.7 mu M. Using the maximum plasma concentration of ppt (C-max), the alteration of area under the curve (AUC) of AZT was 6 %. All these results provide important information for understanding ginseng-AZT interaction. However, considering the complication of herbs and individuals, the in vitro-in vivo extrapolation (IV-IVE) results should be explained with more caution.