title: Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.
abstract: In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors.forename: Tammam
authors.initials: T
authors.lastname: Alama
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Katsumi
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakane
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan. Electronic address: yamamoto@mb.kyoto-phu.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002118:Calcium / Q000097:blood; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005079:Excipients / Q000737:chemistry*; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005452:Fluoresceins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D003911:Dextrans; D005079:Excipients; D005452:Fluoresceins; D010455:Peptides; D011506:Proteins; D013501:Surface-Active Agents; C015219:fluorescein isothiocyanate dextran; C024098:6-carboxyfluorescein; D002116:Calcitonin; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium
keywords: Absorption enhancer; Calcitonin; Gemini surfactant; Intestinal absorption; Peptide drug; Poorly absorbed drug