Division of Clinical Pharmaceutics, Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
Eur J Drug Metab Pharmacokinet. 2020 Oct;45(5):645-652. doi: 10.1007/s13318-020-00631-7.
Generic drugs are generally used worldwide because of affordability compared to brand-name drugs. One of the main differences between brand-name and generic drugs is pharmaceutical excipients. We previously reported the effects of pharmaceutical excipients on the membrane permeation of drugs via the paracellular and transcellular routes, which are passive transport routes. P-glycoprotein (P-gp) is a typical ATP-binding cassette transporter and is mostly responsible for drug-drug interactions involving transporters. In the present study, rhodamine 123 (Rho123) was selected as the P-gp substrate, and the effects of pharmaceutical excipients on its membrane transport in the rat jejunum and ileum were examined.
Twenty major pharmaceutical excipients widely used in the pharmaceutical industry were selected. The in vitro diffusion chamber method using the rat jejunum and ileum was employed to investigate the effects of pharmaceutical excipients on the membrane permeation of Rho123.
The results obtained showed that the membrane permeability of Rho123 significantly (P < 0.05) changed under certain dosage conditions of pharmaceutical excipients such as sodium carboxymethyl starch, pullulan, glyceryl monostearate and so on. Furthermore, the effects of pharmaceutical excipients were site specific in the small intestine.
The present results demonstrated that some pharmaceutical excipients altered the membrane permeability of Rho123 in the rat small intestine.
与品牌药相比，通用药物具有价格优势，因此在全球范围内得到广泛使用。品牌药和仿制药的主要区别之一在于药用辅料。我们之前报道了药用辅料对药物通过细胞旁和细胞内途径（即被动转运途径）的膜渗透的影响。P-糖蛋白（P-gp）是一种典型的三磷酸腺苷结合盒转运蛋白，主要负责涉及转运体的药物-药物相互作用。在本研究中，我们选择罗丹明 123（Rho123）作为 P-gp 的底物，研究了药用辅料对其在大鼠空肠和回肠中的膜转运的影响。
选择了 20 种在制药行业中广泛使用的主要药用辅料。采用大鼠空肠和回肠体外扩散室法，考察了药用辅料对 Rho123 膜透过性的影响。
结果表明，在某些药用辅料（如羧甲基淀粉钠、普鲁兰、单硬脂酸甘油酯等）的一定剂量条件下，Rho123 的膜透过性显著（P < 0.05）改变。此外，药用辅料在小肠中的作用具有部位特异性。
本研究结果表明，一些药用辅料改变了 Rho123 在大鼠小肠中的膜透过性。
