查找使用阿拉丁产品的科研文献

Inhibition of human UDP-glucuronosyltransferase enzyme by belinostat: Implications for drug-drug interactions

Xiaoyu Wang,Zhe Wang,Zhen Wang,Xiuyuan Chen,Hang Yin,Lili Jiang,Jun Cao,Yong Liu

Belinostat is a pan-histone deacetylase (HDAC) inhibitor which recently approved for the treatment of relapsed/refractory Peripheral T-cell lymphomas (PTCL). To assess drug-drug interactions (DDIs) potential of belinostat via inhibition of UDP-glucuronosyltransferases (UGTs), the effects of belinostat on UGTs activities were investigated using the non-selective probe substrate 4-methylumbelliferone (4-MU) and trifluoperazine (TFP) by UPLC–MS/MS. Belinostat exhibited a wide range of inhibition against UGTs activities, particularly a potent non-competitive inhibition against UGT1A3, and weak inhibition against UGT1A1, 1A7, 1A8, 2B4 and 2B7. Further, in vitro – in vivo extrapolation (IVIVE) approaches were used to predict the risk of DDI arising from inhibition of UGTs. Our data indicate that the intravenous infusion of belinostat at clinical available dose can contribute a significant increase to the AUC of co-administrated drugs primarily cleared by UGT1A3 or UGT1A1, which will result in potential DDIs. In contrast, oral administrated belinostat is unlikely to cause significant DDIs through inhibition of glucuronidation.

In vitro characterization of belinostat glucuronidation: demonstration of both UGT1A1 and UGT2B7 as the main contributing isozymes

Dong Dong,Tianpeng Zhang,Danyi Lu,Jie Liu,Baojian Wu