Pharmacokinetics of tetramethylpyrazine in rat blood and brain using microdialysis

Since the central nervous acting agent, tetramelhylpyrazine, is reported to have appreciable blood-brain barrier penetrability, a design allowing simu ltaneous and continual monitoring of drug concentrations in blood and brain was employed to study the distribution of intravenously administered tetra methylpyrazine (10 mg kg(-1)). The system consisted of two microdialysis pr obes, each optimally constructed for sampling of the respective body fluids . inserted into the right jugular vein and striatum of male Sprague-Dawley rats. The probes were perfused with appropriate media at rates optimized fo r recovery. Dialysates were automatically collected using a microfraction c ollector and drugs were analyzed by high performance liquid chromatography (HPLC) with ultra violet (UV) detection. Results indicate that both blood a nd brain pharmacokinetics of unbound tetramethylpyrazine fit best to a two- compartment model. The elimination half-life of tetramethylpyrazine in rat blood and brain were 82.1 and 183.6 min. respectively. Increasing brain/blo od concentration ratios suggested that tetramethyl pyrazine effectively pen etrated the blood-brain barrier. (C) 2001 Elsevier Science B.V. All rights reserved.