20(S)-Protopanaxatriol (Ppt) Exhibits Inhibition Towards UDPGlucuronosyltransferase (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...

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Autores principales: Xing, Jin, Che, Wen
Formato: Articulo Comunicacion
Lenguaje:Inglés
Publicado: 2012
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/20209
http://www.latamjpharm.org/resumenes/31/4/LAJOP_31_4_2_4.pdf
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Sumario: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 (Ki ) was determined to be 24.7 μM. Using the maximum plasma concentration of ppt (Cmax ), 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.