Benny M Amore | PubMed Health

PubMed2004

Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat.

The relationship of rotatable bond count (N(rot)) and polar surface area (PSA) with oral bioavailability in rats was examined for 434 Pharmacia compounds and compared with an earlier report from Veber et al. (J. Med. Chem. 2002, 45, 2615). N(rot) and PSA were calculated with QikProp or Cerius2. The resulting correlations depended on the calculation method and the therapeutic class within the data superset. These results underscore that such generalizations must be used with caution.

Administration, Oral↗

PubMed2002

Predicting drug absorption: how nature made it a difficult problem.

Significant recent work has focused on predicting drug absorption from structure. Several misperceptions regarding the nature of absorption seem to be common. Among these is that intestinal absorption, permeability, fraction absorbed, and, in some cases, even bioavailability, are equivalent properties and can be used interchangeably. A second common misperception is that absorption, permeability, etc. are discrete, fundamental properties of the molecule and can be predicted solely from some structural representation of the drug. In reality, drug absorption is a complex process dependent upon drug properties such as solubility and permeability, formulation factors, and physiological variables, including regional permeability differences, pH, lumenal and mucosal enzymology, and intestinal motility, among others. This article will explore the influence of these different variables on drug absorption and the implications with regards to attempting to develop predictive drug absorption algorithms.

Administration, Oral↗