Ferguson's Principle and the Prediction of Fatal Drug Levels in Blood

The median fatal concentrations (EC50) of various types of drugs are shown to be determined solely by their aqueous solubilities (S). Among the test substances, EC50 values show a range of 2000-fold, whereas the ratio EC50/S is essentially constant. This behaviour is typical of 'Ferguson substances', and enables the fatal toxicity of other (depressant) drugs and related compounds to be calculated. The mean relative saturation (EC50/S) is 0.006, a value which shows that humans are more sensitive to narcotic agents than are the lower animals. The Ferguson principle provides a broad framework for quantitative structure-activity relations in fatal drug toxicity. The empirical Hansch equation can be derived from the same thermodynamic concept of free energy which underlies the Ferguson principle.