Enteral absorption of octreotide: absorption enhancement by polyoxyethylene-24-cholesterol ether

1. The somatostatin octapeptide-analogue octreotide was absorbed as an intact peptide from the gastro-intestinal tract with an absolute bioavailability of about 0.3% in rats. Administration of octreotide in the presence of polyoxyethylene (24)-cholesterol-ether (POECE) resulted in an about 23 fold increase of bioavailability. 2. In vitro studies with Caco-2 cells showed a dose-dependent increase in octreotide permeation with increasing doses of coadministered POECE. The use of [3H]-polyethyleneglycol (PEG) 4000 as an extracellular marker also indicated that higher doses of POECE may partly enhance paracellular transport of macromolecules. 3. By means of fluorescence microscopy it was shown that transepithelial transport of the fluorescent octreotide analogue (4-nitrobenzo-2-oxa-1,3-diazol [NBD] labelled octreotide) was enhanced by the addition of POECE. Besides an increased enterocyte uptake, there was evidence of enhanced partition of NBD-octreotide into the intercellular space between enterocytes after co-administration of POECE. In addition, there appeared to be changes in the hepatic topographic disposition of NBD-octreotide when it was given together with POECE compared with its administration alone. 4. In a study in healthy volunteers, 16 mg POECE significantly enhanced by 8 fold the absorption of octreotide after oral administration.