Lipophilicity, molecular weight, and drug action: Reexamination of parabolic and bilinear models

Abstract

The effect of molecular weight on drug diffusion and drug action has been described based on the relation D = (RT/6πηN) (4πN/3Mv¯3), an inverse relation between the clearance of drugs through artificial membranes and molecular weights, and apparent correlations between log (1/dose) and log mol. wt. for various central nervous system-acting drugs, anticancer drugs, and water-soluble vitamins. In situ rat jejunum permeability data of various drugs were correlated with log P (octanol–buffer) and log mol. wt. A parabolic equation of log P combined with log mol. wt. proposed previously was shown to give significant correlations for hydrolysis data of amides and antifungal data of amines. This model is mathematically simpler and easier to interpret than the more complex curvilinear and bilinear models.