Nasal bioavailability of peptide T in rabbits: absorption enhancement by sodium glycocholate and glycofurol

The aim of the present study was to investigate the absolute nasal bioavail ability of Peptide T from aqueous formulations containing sodium glycochola te, an absorption enhancer with known effect on epithelial tight junctions, and/or glycofurol in a crossover study in rabbits. Additionally, the rever sibility of the absorption enhancing effect of sodium glycocholate was stud ied by applying enhancer and peptide T with different time intervals and ca lculating 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 bioavai lability of Peptide T in water (control formulation), 5% glycofurol, 5% gly cofurol+ 1% sodium glycocholate and sodium glycocholate was 5.9, 22, 29 and 59%, respectively. As indicated by the differences in t(max), C-max and ti me-concentration profiles different patterns of Peptide T absorption were s een 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 concl uded, that nasal absorption of Peptide T in rabbits was effectively enhance d by co-administration of sodium glycocholate, which also provided very fas t absorption rates as well as a relatively short lasting effect of the abso rption enhancing effect. Co-administration of glycofurol leads to enhanced and prolonged absorption of the peptide. Combining the two enhancers did no t lead to increased peptide T absorption compared to 5% glycofurol alone. ( C) 2001 Elsevier Science BY. All rights reserved.