School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Eur J Pharm Sci. 2018 Jul 1;119:62-69. doi: 10.1016/j.ejps.2018.04.002. Epub 2018 Apr 6.
Absorption mechanism of edaravone (EDR) was studied to inform the preparation of gastric retention pellets with the aim to enhance its oral bioavailability. Three different models, namely, Caco-2 cells model, in situ single-pass intestinal perfusion model, and everted gut sac model in rats, were employed to characterize the gastrointestinal absorption kinetics of EDR. And it was found that passive transfer plays a vital role for the transport of EDR, and acidic condition is preferable for EDR absorption. Further, it is likely that EDR acts as a substrate for P-glycoprotein and multidrug-resistance protein. And hence, an orally available gastric retention pellets were developed accordingly. Pharmacokinetic experiments performed with rats and beagles showed that the absolute bioavailability of EDR solution and enteric-coated pellets following oral administration were 33.85% ± 2.45% and 7.64% ± 1.03%, indicating that stomach absorption is better than intestinal adsorption for EDR. However, the gastric retention pellets resulted in 68.96% absolute bioavailability and about 200% relative bioavailability in comparison to EDR solution, which was 9 times that of enteric-coated pellets. The present work demonstrates that gastric retention pellets has excellent potential as oral administration route for EDR.
研究了依达拉奉（EDR）的吸收机制，旨在制备胃滞留丸，以提高其口服生物利用度。本研究采用三种不同的模型，即 Caco-2 细胞模型、在体肠单向灌流模型和大鼠外翻肠囊模型，来表征 EDR 的胃肠道吸收动力学。研究结果表明，被动转运对 EDR 的转运起着至关重要的作用，酸性条件有利于 EDR 的吸收。此外，EDR 可能作为 P 糖蛋白和多药耐药蛋白的底物。因此，开发了一种口服胃滞留丸。用大鼠和比格犬进行的药代动力学实验表明，EDR 溶液和肠溶包衣丸口服后的绝对生物利用度分别为 33.85%±2.45%和 7.64%±1.03%，表明 EDR 的胃吸收优于肠吸收。然而，与 EDR 溶液相比，胃滞留丸的绝对生物利用度为 68.96%，相对生物利用度约为 200%，是肠溶包衣丸的 9 倍。本研究表明，胃滞留丸作为 EDR 的口服给药途径具有巨大的潜力。
