Pharmacokinetic and pharmacodynamic analyses of trazodone in rat striatum by in vivo microdialysis.

The aim of this study was to investigate the brain pharmacokinetics and pharmacodynamics of trazodone. Sensitive microbore high-performance liquid chromatographic methods with electrochemical detection (LC-ED) were developed for the determination of trazodone, serotonin (5-HT), and their respective metabolites. The feasibility of microdialysis coupled with LC-ED system for direct analysis of these compounds in the rat striatum was investigated. Striatal dialysates were automatically injected onto a cyano microbore column, through an on-line injector, for the determination of trazodone and its metabolite or onto a reversed phase microbore column for the determination of 5-HT and its metabolite. A monophase phenomenon with a first-order elimination rate constant was observed for trazodone. The brain pharmacokinetics of trazodone appear to conform to a one-compartment model. Surprisingly, no significant changes in striatal 5-HT or its metabolite were observed following the same dosage and time course. The present results suggest that brain microdialysis methods may be applicable to pharmacokinetic and pharmacodynamic studies of psychotrophic agents.