Thermodynamic Analysis of Structure-Activity Relationships of Drugs: Prediction of Optimal Structure

Lipophilic Character and Biological Activity of Drugs II: The Parabolic Case

“…The thermodynamic model (134) considers the case where, under certain conditions (for example, in a closed system of isolated tissue in uitro), one may approach rather close to equilibrium between drug in solution and drug on the sites of action. Generally, under such conditions (1) one can expect to find a high log Po (4-6) with a "linear" relationship between log 1/C and log P. However, Higuchi and Ravis (134) showed that even under equilibrium conditions, one can expect to find "parabolic" relationships between log l/C and log P. This time-independent model assumes that equilibrium or better quasiequilibrium conditions obtain (by definition, living systems are never at equilibrium). Their model is developed as follows :…”

General Linearized Biexponential Model for QSAR Data Showing Bilinear-Type Distribution

“…LinBiExp can also be considered a generalization of the equilibrium model of Higuchi and Davis derived for congeneric drugs 80 and under somewhat simplified conditions equivalent with…”

“…The schematic model ( Fig. 2) represents an abstract generalization of the alternative aqueous-lipid compartmental models used to model biphasic behavior both in static equilibrium/probability 20,21,79,80 or dynamic (kinetic) [81][82][83] frameworks. Obviously any kind of (theoretically justifiable) descriptor can be used as x (x); for example, size descriptors, such as volume, surface, molecular weight, or even number of atoms in a congener series, lipophilicity descriptors such as log P, electronic descriptors such as s, or other parameters such as pK a can all provide suitable x values.…”

No Effect of Albumin on the Dermal Absorption Rate of Hydrocortisone 21-Butyrate, Permethrin or Diflunisal in the Isolated, Single-Pass Perfused Rabbit Ear

“…Extreme care for the chemical purity of such substrates should be consid ered. Higuchi and Davis [15] have reported theoretical calculations on the lipophilicity of a given compound and its pharmacodynamic activity. They postulated that a high lipophil icity, or a distribution coefficient >1,000, would lead to a decrease in access to the recep tor site through a biological membrane.…”