Fujita T, Muranishi S
Department of Biopharmaceutics, Kyoto Pharmaceutical University.
Nihon Rinsho. 1998 Mar;56(3):589-94.
Oral bioavailability of biologically active peptides and proteins is generally very low because they are extensively degraded by peptidases and proteases in the gastrointestinal tract and impermeable through the intestinal mucosal membrane. Consequently, although clinical application of peptide drugs is limited to administration by injection, such frequent subjects the patients to considerable pain, and there is also possibility of the manifestation of serious side effects. Therefore various approaches have been examined to overcome the delivery problems of peptide drugs. These approaches include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to modify the peptide molecules to produce prodrugs and analogs, (3) to develop an administration method for peptides that can serve as an alternative to oral and injection administration and (4) to use the dosage forms to these peptide drugs. In this paper, we introduce the approaches (1)-(3) and demonstrate that transmucosal absorption of various biologically active peptides and proteins could be improved by using these approaches. These approaches therefore may give us basic information to improve the intestinal absorption of peptide and protein drugs.
生物活性肽和蛋白质的口服生物利用度通常非常低，因为它们在胃肠道中会被肽酶和蛋白酶广泛降解，并且无法透过肠黏膜。因此，尽管肽类药物的临床应用仅限于注射给药，但这种给药方式常常使患者承受相当大的痛苦，而且还可能出现严重的副作用。因此，人们研究了各种方法来克服肽类药物的递送问题。这些方法包括：（1）使用吸收促进剂和蛋白酶抑制剂等添加剂；（2）修饰肽分子以制备前药和类似物；（3）开发一种可替代口服和注射给药的肽类给药方法；（4）使用这些肽类药物的剂型。在本文中，我们介绍了方法（1）-（3），并证明使用这些方法可以提高各种生物活性肽和蛋白质的经黏膜吸收。因此，这些方法可能为我们提供改善肽类和蛋白质药物肠道吸收的基础信息。
