Fan Hui-rong, Ci Xiao-yan, Li Wei, Zeng Yong, Yi Xiu-lin, Si Duan-yun, Liu Chang-xiao, Liang Guang-yi
Yao Xue Xue Bao. 2016 Aug;51(8):1233-9.
Bentysrepinine (Y101), a derivative of phenylalanine dipeptide, is a novel drug candidate for the treatment of hepatitis B virus (HBV) infection. Our previous preclinical pharmacokinetic study showed that its in vivo absorption and distribution characteristics were probably related to transmembrane transport after Y101 was administered intragastically in rats. In this study, Caco-2 and MDCK-MDR1 cell models were used to investigate interactions between Y101 and P-gp through the apparent permeation coefficient (P(app)) and efflux ratio (RE); the results showed that Y101 was a substrate of P-gp. In addition, gene-transfected cell models, HEK293-h OATP1B1, HEK293-h OATP2B1 and CHO-PEPT1 were used to evaluate the affinity to OATP1B1, OATP2B1 and PEPT1. The results suggest that Y101 has a weak inhibitory effect on OATP1B1 and OATP2B1, and Y101 may not be substrates of OATP1B1, OATP2B1 or PEPT1. The above results can be used to explain the in vivo absorption and distribution characteristics, and to provide a scientific basis for the further development of Y101.
苯丙氨酸二肽衍生物本替斯瑞平（Y101）是一种治疗乙型肝炎病毒（HBV）感染的新型候选药物。我们之前的临床前药代动力学研究表明，在大鼠体内胃内给予Y101后，其体内吸收和分布特征可能与跨膜转运有关。在本研究中，使用Caco-2和MDCK-MDR1细胞模型通过表观渗透系数（P(app)）和外排率（RE）研究Y101与P-糖蛋白之间的相互作用；结果表明Y101是P-糖蛋白的底物。此外，使用基因转染细胞模型HEK293-h OATP1B1、HEK293-h OATP2B1和CHO-PEPT1评估对OATP1B1、OATP2B1和PEPT1的亲和力。结果表明Y101对OATP1B1和OATP2B1具有较弱的抑制作用，且Y101可能不是OATP1B1、OATP2B1或PEPT1的底物。上述结果可用于解释体内吸收和分布特征，并为Y101的进一步开发提供科学依据。
