Development of predictive retention - Activity relationship models of tricyclic antidepressants by micellar liquid chromatography

The distribution of tricyclic antidepressants from plasma to brain, where t hese drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It co uld be expected that all the molecular features that: condition the transpo rt processes (mainly hydrophobicity and molar total charge) also control th e pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, a nd benzodiazepines. In this paper, the relationships between the capacity f actor in MLC and some pharmacokinetic parameters and biological responses o f tricyclic antidepressants are studied. Predictive regression models for t he estimation of these parameter values, using the logarithm of the retenti on data (log k) as independent variable, are also proposed.