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Archive > Volume 4 Issue 2 > 2012,4(2):118-125. DOI:10.3969/j.issn.1674-6384.2012.02.005 Prev Next

Original articles

In vitro Metabolism of Strychnine by Human Cytochrome P450 and Its Interaction with Glycyrrhetic Acid

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    摘要:


    Abstract:
    Objective To investigate the metabolism of strychnine (STN) and the metabolic interaction between STN and glycyrrhetic acid (GA) in vitro. Methods Human liver microsomes (HLM) and human recombinant cytochrome P450 (CYP) isoforms were employed to study the metabolism of STN and the metabolic interaction of STN with GA in vitro. Results In HLM, the Km, Vmax, and clearance of STN were 88.50 μmol/L, 0.88 nmol/(mg?min), and 9.93 mL/(mg?min), respectively. STN was metabolized mainly by CYP3A4. However, STN noncompetitively inhibited CYP3A4-catalyzed testosterone 6β-hydroxylation with IC50 value of 5.9 μmol/L and Ki value of 5.5 μmol/L. Moreover, GA competitively inhibited STN metabolism with IC50 value of 10.6 μmol/L and Ki value of 17.7 μmol/L. Conclusion Although STN is mainly metabolized by CYP3A4 in vitro, STN has noncompetitive inhibition on CYP3A4-catalyzed testosterone 6β-hydroxylation. Moreover, GA could competitively inhibit STN metabolism. The present work is helpful to elucidate the metabolic interaction between STN and GA.

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    Project Supported:
    National Natural Science Foundation of China (30630075)

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