title: Nasal bioavailability of peptide T in rabbits: absorption enhancement by sodium glycocholate and glycofurol.
abstract: The aim of the present study was to investigate the absolute nasal bioavailability of Peptide T from aqueous formulations containing sodium glycocholate, an absorption enhancer with known effect on epithelial tight junctions, and/or glycofurol in a crossover study in rabbits. Additionally, the reversibility of the absorption enhancing effect of sodium glycocholate was studied by applying enhancer and peptide T with different time intervals and calculating Area Under the Curve of the peptide in plasma. It was shown that the bioavailability of Peptide T was significantly enhanced when glycofurol or sodium glycocholate was added to a nasal formulation. The nasal bioavailability of Peptide T in water (control formulation), 5% glycofurol, 5% glycofurol+1% sodium glycocholate and 1% sodium glycocholate was 5.9, 22, 29 and 59%, respectively. As indicated by the differences in t(max), C(max) and time-concentration profiles different patterns of Peptide T absorption were seen from the vehicles containing glycofurol and sodium glycocholate. In the reversibility study, the enhancing effect of sodium glycocholate on nasal absorption of Peptide T was found to be reversible within 4 h. It was concluded, that nasal absorption of Peptide T in rabbits was effectively enhanced by co-administration of sodium glycocholate, which also provided very fast absorption rates as well as a relatively short lasting effect of the absorption enhancing effect. Co-administration of glycofurol leads to enhanced and prolonged absorption of the peptide. Combining the two enhancers did not lead to increased peptide T absorption compared to 5% glycofurol alone.
authors.affiliation: Department of Pharmaceutics, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: M A
authors.initials: MA
authors.lastname: Bagger
authors.forename: H W
authors.initials: HW
authors.lastname: Nielsen
authors.forename: E
authors.initials: E
authors.lastname: Bechgaard
mesh_terms: D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D006000:Glycocholic Acid / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D015717:Peptide T / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011817:Rabbits; D013268:Stimulation, Chemical
chemical_list: D015717:Peptide T; D011092:Polyethylene Glycols; D006000:Glycocholic Acid; C018557:glycofurol