possessing a higher ratio, i.e., thiopental and thiamylal, become concentrated to a higher degree in the body lipids than do barbital or metharbital and might be expected to be ultrashort acting.
In considering these solubility data in total, an approximate correlation has been observed between the lipophilic nature of the various barbiturate analogs and their therapeutic action. One must view this study with proper perspective in relation to the numerous other physical and chemical properties as well as the various biopharmaceutical parameters which all contribute to the variation in the final therapeutic activity possessed by the members of this series. The net result of the complex interaction of these and other factors determines the type and degree of the pharmacological activity involved.
The underlying concept of the pH-partition hypothesis as an approximate model would seem to be confirmed. However, such phenomena as binding, detoxification, active or passive diffusion, and complexation would play important roles in biologicaI readouts which were not patternized or aberrant in behavior.
It is anticipated that severat studies on the barbiturates and sub fonamides relative to solubility and partitioning will be undertaken in these laboratories and will be the subject of future communications.