Predicting the Intestinal Absorption of Anionic Drugs from Their Physicochemical Properties

Abstract

A method for predicting the intestinal absorption of anionic drugs by measuring their physicochemical properties (organic solvent/buffer partition coefficients, hydrogen bonding and diffusion rate across silicone membrane) was investigated. The absorption rates of ten anionic drugs, which were mainly non-steroidal anti-inflammatory agents, were measured in-situ by a rat intestinal single-pass perfusion technique. A poor correlation between the absorption rate and the partition into octanol was observed, although the absorption rate showed a tendency to increase when the partition coefficient increased. On the other hand, the technique of determining the permeation rate across silicon membrane, which comprises a diffusion process, gave a good correlation with the in-situ absorption results. The effects of permeant size (molecular volume or molecular weight) and hydrogen bonding were also investigated. When these two factors were considered together with the permeation rate across a silicone membrane, excellent regression coefficients were obtained. These results suggest that the permeation rate across a silicone membrane, permeant size and hydrogen bonding are valuable measures for predicting the absorption behaviour of anionic drugs.