Absorption of an RGD peptide (SK & F 106760) following intratracheal administration in rats

Abstract

The objective of this study was to determine the bioavailability of an RGD peptide, SK & F 106760, following intratracheal administration in a rat model. These results provide information pertinent to determining the utility of this route for peptide delivery in general and specifically for the RGD class of peptides. The data indicate that the area under the plasma concentration versus time curve for SK & F 106760 following intratracheal administration in the rat is linearly related to dose (3 and 10 mg/kg) and bioavailability is approx. 20%. The T max values after intratracheal dosing were 55.0 and 16.5 min at 3 and 10 mg/kg, respectively. By comparison, bioavailability of SK & F 106760 administered intraduodenally in the rat is approx. 0.5%. The rate of absorption varied with the pH of the dosing solution. T max values decreased from 16.5 min at pH 5.5 to 4.4 min at pH 2.5 and the corresponding C max increased from 2.8 to 7.8 μg/ml. However, this change in dosing solution pH had no effect on the extent of absorption. From the permeability/bioavailability data generated in this study, together with information concerning the dosage and dosage regimen required, rational decisions regarding formulation approaches and selection of route of administration can be made. These data, together with reports from the literature, clearly demonstrate that absorption of peptides via the lung may be a viable option for systemic delivery.