Pharmacokinetics of Vincamine in Rat by Microdialysis

• Main Authors: Ying-Ping Juan, 阮盈萍
• Other Authors: Tung-Hu Tsai
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/28196449790052159577

碩士 === 國立陽明大學 === 傳統醫藥學研究所 === 91 === Abstract Vincamine is an alkaloid compound derived from the Vinca minor plant. As little is known concerning its detailed pharmacokinetics, this study focused 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 liquid chromatography coupled with microdialysis for the simultaneous determination of unbound vincamine in rat blood and brain. Pharmacokinetic parameters of vincamine were derived using non-compartmental model. Microdialysis probes were simultaneously inserted into the jugular vein toward right atrium and brain hippocampus of male Sprague-Dawley rats for sampling in biological fluids following the administration of vincamine (10, 30 and 60 mg/kg) through the femoral vein. These results indicate that vincamine appears linear pharmacokinetic manner in the dosage ranges (10-60 mg/kg). In addition, cyclosporin A (a P-glycoprotein transport modulator) was used to explore the blood-brain barrier (BBB) transportation mechanism of vincamine. The P-glycoprotein inhibitor cyclosporin A was used to help delineate its roles. The study design consisted of two groups of six rats in parallel: control rats which received vincamine alone and the cyclosporin A treated-group in which the rats were injected cyclosporin A 10 min prior to vincamine administration. The decline of vincamine in the hippocampus and blood suggested that there was rapid exchange and equilibration between the peripheral compartment and the central nervous system. Vincamine was able to penetrate the BBB. In the presence of cyclosporin A, vincamine level in brain was significantly increased which reveal that the BBB transport mechanism may be regulated by P-glycoprotein. The total concentrations of vincamine were measured in plasma as well as the total concentrations in different brain regions (cerebral cortex, cerebellum, brain stem, hippocampus, striatum and the rest of region). After 20 min of vincamine administration, the plasma protein binding of vincamine was 44 % and the hippocampus brain tissue protein binding was 92 %, which was calculated by the concentration of unbound & total form. The brain regional concentration of vincamine was uneven distribution and the hippocampus concentration (22.5 ± 3.1 mg/g) was about 8.6-fold higher than that in plasma (2.6 ± 0.2 mg/ml). In conclusion, we have developed a fast and sensitive liquid chromatographic system coupled with microdialysis to measured unbound vincamine in rat blood and brain. The pharmacokinetics of vincamine appears linearity. Vincamine was able to penetrate BBB, which may be regulated by the P-glycoprotein.