Improvement of transmucosal absorption of biologically active peptide drugs

Authors
Citation
A. Yamamoto, Improvement of transmucosal absorption of biologically active peptide drugs, YAKUGAKU ZA, 121(12), 2001, pp. 929-948
Citations number
81
Language
GIAPPONESE
art.tipo
Review
Categorie Soggetti
Pharmacology & Toxicology
Journal title
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
ISSN journal
0031-6903 → ACNP
Volume
121
Issue
12
Year of publication
2001
Pages
929 - 948
Database
ISI
SICI code
0031-6903(200112)121:12<929:IOTAOB>2.0.ZU;2-V
Abstract
Peptide and protein drugs are becoming a very important class of therapeuti c agents. However, the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the g astrointestinal tract or impermeable through the intestinal mucosa. For the systemic delivery of the peptide and protein drugs, parenteral administrat ion is currently required to achieve their therapeutic activities. However, this administration is poorly accepted by patients and may cause allergic reactions and serious side effects. Therefore, various approaches have been examined to overcome the delivery problems of these peptides when they are administered into the gastrointestinal tract and other mucosal sites. Thes e approaches include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to develop an administration method for peptides t hat can serve as an alternative to oral and injection administration, (3) t o modify the molecular structure of peptide and protein drugs to produce pr odrugs and analogues, and (4) to use the dosage forms to these peptide drug s. In this study, we demonstrated that the transmucosal absorption of vario us peptides including insulin, calcitonin, tetragastrin and thyrotropin rel easing hormone (TRH) could be improved by the use of these approaches. Ther efore, these approaches may give us basic information to improve the transm ucosal absorption of peptide and protein drugs.