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YANG Yang, LI Jing, XIAO Tao, LI Tao, FU Xiaozhong. In vitro metabolism and stability of adefovir mixed phosphonate derivative Q3-I2[J]. Journal of China Pharmaceutical University, 2018, 49(6): 699-705. DOI: 10.11665/j.issn.1000-5048.20180610
Citation: YANG Yang, LI Jing, XIAO Tao, LI Tao, FU Xiaozhong. In vitro metabolism and stability of adefovir mixed phosphonate derivative Q3-I2[J]. Journal of China Pharmaceutical University, 2018, 49(6): 699-705. DOI: 10.11665/j.issn.1000-5048.20180610
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In vitro metabolism and stability of adefovir mixed phosphonate derivative Q3-I2

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  • A, UPLC-QTOF-MS/MS and UPLC-MS/MS were used to investigate the derivative of adefovir mixed phosphonate Q3-I2. Stability and in vitro metabolites of Q3-I2, and the control drug adefovir dipivoxil were co-inculbated with artificial gastric juice, artificial intestinal juice, rat blank plasma and rat liver microsomes, using UPLC-MS/MS and UPLC-QTOF-MS/MS measure the residual concentration of the compounds in each incubation system and the metabolites in the liver microsomal system, respectively, and calculate the half-life and clearance rate by the substrate elimination method. The compounds designed and synthesized in this experiment are stable in the gastrointestinal tract, prolonging t1/2 of plasma and liver microsomes and rapidly degrading the active meta-bolites. In the liver microsomal system, a total of 8 metabolites were detected by positive and negative ion mode, including hydrolysis, oxidation, acetylation, and glucuronidation.
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  • [1]
    Sweet DH,Bush KT,Nigam SK.The organic anion transporter family:from physiology to ontogeny and the clinic[J].Am J Physiol Renal Physiol,2001,281:197-205.
    [2]
    Xiang D,Zhang CL,Yu ZQ,et al.Research progress of bile acid transporters[J].J China Pharm Univ(中国药科大学学报),2017,52(3):567-573.
    [3]
    Enhsen A,Kramer W,Wess G.Bile acids in drug discovery[J].J Drug Discov Today,1998,3:409-418.
    [4]
    Su H,Chen Y,Fu XZ,et al.Synthesis,antiviral activity and primary hepatocyte uptake of adefovir single L-amino acid and bile acid ester derivatives[J].J China Pharm Univ(中国药科大学学报),2016,47(3):264-268.
    [5]
    Zhang WZ,Yang Y,Chen Y,et al.Synthesis and biological eva-luation of mixed phosphonates derivatives of adefovir with hepatotrophic property[J].J China Pharm Univ(中国药科大学学报),2018,49(1):39-47.
    [6]
    Haufroid V,Buchet JP,Gardinal S,et al.Cytochrome P4502E1 phenotyping by the measurement of the chlorzoxazone metabolic ratio:assessment of its usefulness in Workers Exposed To styrene[J].Int Arch Occup Environ Health,2002,75(7):453-458.
    [7]
    Mcfadyen MC,Breeman S,Payne S,et al.Immuno-histochemical localization of cytochrome P450 CYP1B1 in breast cancer with monoclonal antibodies specific for CYP1B1[J].J Histochem Cytochem,1999,47(11):1457-1464.
    [8]
    Baranczewski P,Stanczak A,sundbergk,et al.Introduction to in vitro estimation of metabolic stability and drug interactions of vew chemical entities in drug discovery and development[J].J Pharacol Rep,2006,58(4):453-472.
    [9]
    Qin ZF,Li SS,Yao ZH,et al.Metabolic profiling of corylin in vivo and in vitro[J].J Pharm Biomed Anal,2018,15(5):157-168.
    [10]
    Ettmayer P,Amidon GL,Clement B,et al.Lessons learned from marketed and investigation pro-drugs[J].J Med Chem,2004,47(10):2393-2404.
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