title: The effect of a drug-delivery system consisting of soybean phosphatidyl choline and medium-chain monoacylglycerol on the intestinal permeability of hexarelin in the rat.
abstract: The aim of this study was to investigate if the effective in-situ permeability (Peff) of a new growth hormone-releasing peptide, hexarelin, along rat intestine was enhanced by a lipid matrix drug-delivery system comprising a mixture of soybean phosphatidyl choline and medium-chain monoacylglycerol (PC-MG). The study was performed with and without a protease inhibitor, Pefabloc SC. To enable better understanding of the mechanism of action of this delivery system we also studied the uptake of a small hydrophilic molecule, atenolol. PC-MG at a concentration of 15 mmol L(-1) increased the jejunal Peff of hexarelin approximately 20-fold, both in the presence and absence of Pefabloc SC, whereas Peff was not increased in the ileum and colon. PC-MG had no effect on the jejunal, ileal and colonic Peff of atenolol. Complete recovery of the non-absorbable molecule PEG 4000 showed that functional intestinal viability was maintained in all experiments. Although the results obtained in this study are promising, pharmacokinetic and toxicological studies are required to investigate if this delivery system is a suitable and safe candidate for improving the oral bioavailability of hexarelin.
authors.affiliation: Department of Pharmacy, University of Uppsala, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Fagerholm
authors.forename: B
authors.initials: B
authors.lastname: Sjöström
authors.forename: J
authors.initials: J
authors.lastname: Sroka-Markovic
authors.forename: A
authors.initials: A
authors.lastname: Wijk
authors.forename: M
authors.initials: M
authors.lastname: Svensson
authors.forename: H
authors.initials: H
authors.lastname: Lennernäs
mesh_terms: D000818:Animals; D001262:Atenolol / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability / Q000187:drug effects; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005989:Glycerides; D006133:Growth Substances / Q000008:administration & dosage / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010713:Phosphatidylcholines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013025:Glycine max; D013450:Sulfones / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D004338:Drug Combinations; D005989:Glycerides; D006133:Growth Substances; D009842:Oligopeptides; D010713:Phosphatidylcholines; D013450:Sulfones; D014361:Trypsin Inhibitors; C086184:hexarelin; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D001262:Atenolol