罗格列酮在大鼠体内药动学及组织分布研究(英文)

Pharmacokinetics and tissues distribution of rosiglitazone in rats

建立并验证一个简单和快速的血浆中罗格列酮RP-HPLC分析方法和提取方法,并将该法应用于罗格列酮体内药动学和组织分布研究.在大鼠给药前和给药后0.083,0.25,0.50,1,2,3,4,6,8,10和24h通过尾静脉采集血样检测,并检测给药1h后各组织的罗格列酮的分布情况.给药后1h,采集大鼠脑脊液,检测脑脊液内罗格列酮是否存在.结果显示,大鼠灌胃给药3mg/kg时,AUC(0-∞)为(1 574.419±332.731)mg.min.L-1,Tmax为(40±10)min,CL/F为0.002L.min-1.kg-1,t1/2为(150.314±44.209)min,Cmax为(6.974±0.877)mg/L.给药1h后,各个组织均有分布.罗格列酮能够透过血脑屏障,给药后1h,通过率为0.004 5%.由此得出结论,罗格列酮在大鼠体内吸收迅速,分布广泛,且能够通过血脑屏障.

A simple,rapid and selective HPLC method was developed and validated to determinate rosiglitazone in rat plasma,tissues and cerebrospinal fluid.Samples were prepared,with a higher extraction recovery（96.72% in plasma,95.63% in tissues and 90.67% in cerebrospinal fluid）,based on a simple methanol protein precipitation.Assay of rosiglitazone was achieved on a reversed-phase C18 column（250 mm× 4.6 mm,5 μm） with a mobile phase consisting of acetonitrile and 20 mmol/L ammonium acetate pH 6.0（53∶47,v/v） at a flow rate of 0.6 mL/min.The method was applied to study pharmacokinetics,distribution of rosiglitazone in rats after a single intragastric administration.The rosiglitazone was rapidly absorbed（Tmax 0.5～1 h） with an elimination half-life of 2.5 hours.The highest levels of the drug were observed in liver and fat while the lowest levels in the brain and spleen.The method was also used for the determination of rosiglitazone in cerebrospinal fluid.The result showed that rosiglitazone can be detected in cerebrospinal fluid,thus providing direct evidence that rosiglitazone can permeate cross blood brain barrier.