Absorption of water-soluble compounds with different molecular weights and[Asu(1.7)]-eel calcitonin from various mucosal administration sites

Citation
A. Yamamoto et al., Absorption of water-soluble compounds with different molecular weights and[Asu(1.7)]-eel calcitonin from various mucosal administration sites, J CONTR REL, 76(3), 2001, pp. 363-374
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF CONTROLLED RELEASE
ISSN journal
0168-3659 → ACNP
Volume
76
Issue
3
Year of publication
2001
Pages
363 - 374
Database
ISI
SICI code
0168-3659(20011019)76:3<363:AOWCWD>2.0.ZU;2-H
Abstract
The absorption of water soluble compounds with different molecular weights, such as phenol red (MW 354), trypan blue (MW 960), fluorescein isothiocyan ate dextrans, (MW 4400 and 9100) was studied in the lung, nasal cavity, buc cal cavity, small and large intestine of rats. For all the compounds, maxim al absorption was observed when administered to the lung. The rank order of absorption of each compound from various administration sites was lung > s mall intestine greater than or equal to nasal cavity greater than or equal to large intestine greater than or equal to buccal cavity. In addition, the relationship between logarithm absorption % of the compounds from various administration sites and logarithm molecular weights of these compounds was examined. The absorption of compounds gradually decreased with increasing molecular weight for each site of administration. Moreover, the absorption of [Asu (1,7)]-eel calcitonin (ECT) from these sites and the effect of 10 m M sodium glycocholate, an absorption enhancer, on its absorption were also investigated in rats. When ECT alone was administered into these sites, the lung had the best absorption site of ECT, followed by the nasal cavity, th e large intestine, the small intestine and the buccal cavity. Therefore, th e absorption of ECT was also dependent on the administration site, although the rank order of absorption % of ECT was different from the other compoun ds. Sodium glycocholate (NaGC) remarkably increased ECT absorption from the small intestine, while we found marginal increase in its absorption from t he lung even in the presence of NaGC. These findings provided useful fundam ental information that might aid in the selection of administration routes for drugs of differing molecular weights including peptide drugs as far as the degree of drug absorption is concerned. (C) 2001 Elsevier Science B.V. All rights reserved.