Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1550 4th Street RH584E, San Francisco, California, 94143-2911, USA.
Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
AAPS J. 2021 Sep 15;23(5):106. doi: 10.1208/s12248-021-00631-8.
P-glycoprotein (P-gp) plays a critical role in drug oral bioavailability, and modulation of this transporter can alter the safety and/or efficacy profile of substrate drugs. Individual oral molecular excipients that inhibit P-gp function have been considered a mechanism for improving drug absorption, but a systematic evaluation of the interaction of excipients with P-gp is critical for informed selection of optimal formulations of proprietary and generic drug products. A library of 123 oral molecular excipients was screened for their ability to inhibit P-gp in two orthogonal cell-based assays. β-Cyclodextrin and light green SF yellowish were identified as modest inhibitors of P-gp with IC values of 168 μM (95% CI, 118-251 μM) and 204 μM (95% CI, 5.9-1745 μM), respectively. The lack of effect of most of the tested excipients on P-gp transport provides a wide selection of excipients for inclusion in oral formulations with minimal risk of influencing the oral bioavailability of P-gp substrates.
P-糖蛋白（P-gp）在药物口服生物利用度中起着关键作用，而这种转运蛋白的调节可以改变底物药物的安全性和/或疗效特征。抑制 P-gp 功能的个体口服分子赋形剂被认为是提高药物吸收的一种机制，但对赋形剂与 P-gp 相互作用的系统评估对于明智地选择专有和仿制药产品的最佳配方至关重要。筛选了 123 种口服分子赋形剂，以评估它们在两种正交基于细胞的测定法中抑制 P-gp 的能力。β-环糊精和亮绿 SF 黄分别被鉴定为中等强度的 P-gp 抑制剂，IC 值分别为 168 μM（95%CI，118-251 μM）和 204 μM（95%CI，5.9-1745 μM）。大多数测试的赋形剂对 P-gp 转运没有影响，这为口服制剂中赋形剂的选择提供了广泛的选择，最小化了影响 P-gp 底物口服生物利用度的风险。
