Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Saudi Pharm J. 2010 Apr;18(2):97-101. doi: 10.1016/j.jsps.2010.02.005. Epub 2010 Feb 13.
Furosemide is a commonly used diuretic which is used in the treatment of edema, congestive heart failure, hypertension and renal failure. Its absorption exhibits inter- and intra-subject variability that can be attributed to many factors including the intestinal efflux pumps such as the P-glycoprotein (P-gp). This study was done due to the great disagreement between what is published in the literature regarding the influence of P-gp on furosemide and at the same time due to the importance of this drug in the treatment of different conditions as described above. In addition, an investigation of the effect of two of the commonly used pharmaceutical excipients (hydroxypropyl β-cyclodextrin [HPβCD] and Tween 80) and also a P-gp inhibitor (verapamil hydrochloride) on the intestinal absorption of this drug were also done.
The study utilized the everted intestinal sacs technique to investigate both the effect of the efflux transporter (P-gp) on furosemide absorption and also the effect of the chosen excipients.
The absorption of furosemide was significantly influenced by the P-gp as confirmed by the everted vis the non-everted sacs together with the verapamil study in which the transport of furosemide was inhibited by verapamil. In addition, Tween 80 was also shown to inhibit the P-gp pump whereas the HPβCD did not significantly influence the efflux of furosemide in this study.
P-glycoprotein and some of the used excipients in the formulation play a very important role in the transport of furosemide and other drugs. Thus excipients that affect the activity of P-gp should be avoided when formulating drugs that are substrate for the P-gp or other efflux pumps.
呋塞米是一种常用的利尿剂，用于治疗水肿、充血性心力衰竭、高血压和肾衰竭。其吸收表现出个体间和个体内的变异性，这可归因于许多因素，包括肠外排泵如 P-糖蛋白（P-gp）。进行这项研究是因为文献中关于 P-gp 对呋塞米的影响存在很大分歧，同时也是因为这种药物在治疗上述不同疾病中的重要性。此外，还研究了两种常用药用辅料（羟丙基-β-环糊精[HPβCD]和吐温 80）和 P-gp 抑制剂（盐酸维拉帕米）对该药物肠吸收的影响。
该研究利用外翻肠囊技术研究外排转运体（P-gp）对呋塞米吸收的影响以及所选辅料的影响。
P-gp 明显影响了呋塞米的吸收，这一点通过外翻囊与非外翻囊的对比以及维拉帕米研究得到了证实，在维拉帕米研究中，呋塞米的转运被维拉帕米抑制。此外，吐温 80 也被证明抑制了 P-gp 泵，而 HPβCD 在本研究中对呋塞米的外排没有显著影响。
P-糖蛋白和制剂中使用的一些辅料在呋塞米和其他药物的转运中起着非常重要的作用。因此，在为 P-gp 或其他外排泵的底物药物配方时，应避免使用影响 P-gp 活性的辅料。
