Correlation between nasal membrane permeability and nasal absorption rate.

The objective of this study was to investigate the relationship between in vitro permeability (Papp) values obtained from isolated nasal tissues and the absorption rates (ka) of the same compounds following nasal administration in animals and humans. The Papp of a set of 11 drug compounds was measured using animal nasal explants and plasma time-concentration profiles for each of the same compounds following intravenous (IV) and intranasal (IN) administration were experimentally determined or obtained from literature reports. The plasma clearance was estimated from the IV plasma time-concentration profiles, and ka was determined from the IN plasma time-concentration profiles using a deconvolution approach. The level of correlation between Papp and ka was established using Pearson correlation analysis. A good correlation (r=0.77) representing a point-to-point relationship for each of the compounds was observed. This result indicates that the nasal absorption for many drug candidates can be estimated from a readily measured in vitro Papp value.