Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Pharmacol Ther. 2020 Jul;211:107537. doi: 10.1016/j.pharmthera.2020.107537. Epub 2020 Mar 20.
The oral bioavailability of hydrophilic and macromolecular drugs is generally poor owing to their poor membrane permeability. For example, peptide and protein drugs are poorly absorbed because of their low stability and poor membrane permeability in the gastrointestinal tract. Consequently, these drugs can be clinically administered only via injection. However, such frequent administration of injections subjects the patients to considerable pain, along with increasing the possibility of serious side effects. Several approaches have been examined to overcome the delivery problems associated with the poorly absorbed drugs. These include (1) use of additives such as absorption enhancers and protease inhibitors, (2) modification of the chemical structure of drugs to produce prodrugs and analogs, (3) application of dosage forms to entrap these poorly absorbed drugs, and (4) development of novel and alternative administration methods (apart from oral and parenteral administration). We examined these approaches and demonstrated their effectiveness in improving intestinal and transmucosal absorption of several poorly absorbed drugs. These approaches may provide useful and basic information to improve the intestinal and transmucosal absorption of poorly absorbed drugs including peptide and protein drugs.
由于亲水性和大分子药物的膜通透性差，其口服生物利用度通常较差。例如，由于在胃肠道中稳定性差和膜通透性差，肽类和蛋白质类药物的吸收较差。因此，这些药物只能通过注射临床给药。然而，这种频繁的注射会给患者带来很大的痛苦，并增加严重副作用的可能性。已经研究了几种方法来克服与吸收不良药物相关的给药问题。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）修饰药物的化学结构以产生前药和类似物；（3）应用剂型来包封这些吸收不良的药物；（4）开发新的和替代的给药方法（除了口服和肠胃外给药）。我们研究了这些方法，并证明了它们在改善几种吸收不良药物的肠道和黏膜吸收方面的有效性。这些方法可能为改善包括肽类和蛋白质类药物在内的吸收不良药物的肠道和黏膜吸收提供有用的基础信息。
