Inhibition of Cytochrome P450 by Nomilin and Obacunone and Potential Mechanism in Human Liver Microsomes
作者： Yao-wen Fan , Yun-long Chen , Jun-xiu Chen , Fang-liang Zhang , Gregory Ondieki
DOI: 10.1016/S1674-6384(17)60107-2
关键词:
摘要: Abstract Objective Nomilin and obacunone are two important limonoids that well known for their anticancer effect. Previous studies showed had inhibitory effect on cytochrome P450 3A4 (CYP3A4). However these effects inconclusive with regards to prediction of potential drug interactions. Methods or was pre-incubated HLMs 30 min. Following 10-fold dilution from the pre-incubation concentration, a second incubation performed in presence NADPH substrates 15 The reaction quenched supernatants were analyzed by chromatography/mass spectrometry. Results In this study, nomilin potent CYP3A4 IC50 values 3.50 6.08 µmol/L, respectively. inhibition time-, concentration- NADPH-dependent manner Ki 2.92 1.25 µmol/L Kinact 0.033 0.078 min−1 These results elucidated they time-dependent inhibitors CYP3A4. Conclusion Concomitant use other drugs may call extra caution purposes clinical safety.
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