Measurement and pharmacokinetics of vincamine in rat blood and brain using microdialysis.

Vincamine is an alkaloid compound derived from the Vinca minor plant. Since little is known concerning its pharmacokinetics and appropriate analytical method, this study focuses on its pharmacokinetics as well the possible roles of the multidrug transporter P-glycoprotein on its distribution and disposition. We develop a rapid and sensitive method using a microdialysis coupled with liquid chromatography for the concurrent determination of unbound vincamine in rat blood and brain. Microdialysis probes were simultaneously inserted into the jugular vein toward heart and brain hippocampus of male Sprague-Dawley rats for sampling in biological fluids following the administration of vincamine (10 and 30 mg/kg) through the femoral vein. Samples were eluted with a mobile phase containing methanol-1% diethylamine (pH 7.15) in water (75:25, v/v) and the flow rate of the mobile phase was 0.7 ml/min. Pharmacokinetic parameters of vincamine were derived using compartmental model. The decline of protein-unbound vincamine in the hippocampus and blood suggested that there was rapid exchange and equilibration between the peripheral compartment and the central nervous system. In the presence of cyclosporine, unbound vincamine levels in both blood and brain were significantly increased.