Predicting Passive Intestinal Drug Absorption: An Interesting Relationship between Fraction Absorbed and Melting Point

Abstract

Oral drug administration remains the most popular route of drug delivery. Absorption of the dissolved drug through the intestinal epithelial membrane is a prerequisite to systemic bioavailability and drug efficacy. In efforts to reduce the long lead times, attrition rates, and costs of drug discovery and development, computational models have been developed to predict the membrane permeability and absorption efficiency of a dosed drug. Many models utilize various molecular descriptors to correlate with in vitro permeability or human intestinal absorption data. It is widely accepted that the two most significant physicochemical properties that control a compound's passive transport process are its aqueous solubility and lipophilicity characteristics.This work will discuss the theoretical background of passive transport, a number of computational models developed to predict in vitro permeability, other models that predict human fraction of dose absorbed, and predicting absorption efficiency relative to a maximum dose. A newly developed prediction method is also presented, that reveals an interesting relationship between fraction absorbed and the melting point of the drug.