Bedada Satish Kumar, Appani Ramgopal, Boga Praveen Kumar
a Drug Metabolism and Pharmacokinetics Division , University College of Pharmaceutical Sciences, Kakatiya University , Warangal , India.
b Department of Pharmaceutical Chemistry , Nethaji Institute of Pharmaceutical Sciences, Kakatiya University , Warangal , India.
Drug Dev Ind Pharm. 2017 Jun;43(6):932-938. doi: 10.1080/03639045.2017.1285310. Epub 2017 Feb 5.
Capsaicin is the main pungent principle present in chili peppers has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro, which may have the potential to modulate bioavailability of P-gp substrates. Therefore, purpose of this study was to evaluate the effect of capsaicin on intestinal absorption and bioavailability of fexofenadine, a P-gp substrate in rats.
The mechanistic evaluation was determined by non-everted sac and intestinal perfusion studies to explore the intestinal absorption of fexofenadine. These results were confirmed by an in vivo pharmacokinetic study of oral administered fexofenadine in rats.
The intestinal transport and apparent permeability (P) of fexofenadine were increased significantly by 2.8 and 2.6 fold, respectively, in ileum of capsaicin treated rats when compared to control group. Similarly, absorption rate constant (K), fraction absorbed (F) and effective permeability (P) of fexofenadine were increased significantly by 2.8, 2.9 and 3.4 fold, respectively, in ileum of rats pretreated with capsaicin when compared to control group. In addition, maximum plasma concentration (C) and area under the concentration-time curve (AUC) were increased significantly by 2.3 and 2.4 fold, respectively, in rats pretreated with capsaicin as compared to control group. Furthermore, obtained results in rats pretreated with capsaicin were comparable to verapamil (positive control) treated rats.
Capsaicin pretreatment significantly enhanced the intestinal absorption and bioavailability of fexofenadine in rats likely by inhibition of P-gp mediated cellular efflux, suggesting that the combined use of capsaicin with P-gp substrates may require close monitoring for potential drug interactions.
辣椒素是辣椒中的主要辛辣成分，已发现其在体外具有P-糖蛋白（P-gp）抑制活性，这可能具有调节P-gp底物生物利用度的潜力。因此，本研究的目的是评估辣椒素对大鼠中P-gp底物非索非那定的肠道吸收和生物利用度的影响。
通过非翻转肠囊和肠道灌注研究进行机制评估，以探究非索非那定的肠道吸收情况。这些结果通过大鼠口服非索非那定的体内药代动力学研究得到证实。
与对照组相比，辣椒素处理的大鼠回肠中，非索非那定的肠道转运和表观渗透率（P）分别显著增加了2.8倍和2.6倍。同样，与对照组相比，用辣椒素预处理的大鼠回肠中，非索非那定的吸收速率常数（K）、吸收分数（F）和有效渗透率（P）分别显著增加了2.8倍、2.9倍和3.4倍。此外，与对照组相比，用辣椒素预处理的大鼠的最大血浆浓度（C）和浓度-时间曲线下面积（AUC）分别显著增加了2.3倍和2.4倍。此外，用辣椒素预处理的大鼠所获得的结果与维拉帕米（阳性对照）处理的大鼠相当。
辣椒素预处理显著增强了大鼠中非索非那定的肠道吸收和生物利用度，可能是通过抑制P-gp介导的细胞外排，这表明辣椒素与P-gp底物联合使用可能需要密切监测潜在的药物相互作用。
