马来酸罗格列酮脉冲型小片胶囊在家犬体内的药物动力学考察

Pharmacokinetics of rosiglitazone maleate pulsatile mini-tablet capsules in dogs

目的建立测定马来酸罗格列酮脉冲小片胶囊家犬体内马来酸罗格列酮含量的荧光检测HPLC方法,并应用于药物动力学研究。方法采用RP-HPLC法。色谱柱:ODS色谱柱;流动相:50 mmol.L-1乙酸胺水溶液(用冰醋酸调节pH 6)-乙腈(体积比50∶50);流速:1 mL.min-1;激发波长:320 nm,发射波长:370 nm;柱温:室温。结果马来酸罗格列酮、甲磺酸多沙唑嗪的保留时间分别为4.8、6.1 min;脉冲小片胶囊给药后分别在1、6、11 h出现3次释药高峰;tmax分别为1、6、11 h,ρmax分别为124.6、111.2、134.4μg.L-1。结论该方法灵敏、快速、准确,操作简便,线性范围宽,可用于马来酸罗格列酮的体内药物动力学研究。

Objective To develop a sensitive and specific HPLC method for determination of rosiglitazone maleate in dog plasma and provide a research method for pharmacokinetic investigation. Methods The HPLC method was used in the experiment. The mobile phase consisted of 50 mmol· L^-1 ammonium acetate （pH = 6）-acetonitrile （ V ： V = 50 ： 50）. HPLC was run at the flow rate of 1.0 mL·min^- 1 and detected by fluorescence absorption at the excitation wavelength of 320 nm as excitation wave and the emission wavelength of 370 nm as emission wave at room temperature. Retention time of rosiglitazone maleate and internal standard were 4.8, 6.1 rain, respectively. Results After the administration of mini-tablet capsules, the maximum plasma levels were reached at the time of 1,6 and 11 h, respectively. The t1/2 and ρmax of the mini-tablet capsules were 1,6, 11 h and 124.6, 111.2,134.4μg· L^- 1, respectively. The relative bioavailability of the minitablet capsules versus the marketed conventional tablets was 100.0 %. Conclusions The established method is proved to be sensitive, rapid and accurate. It is suitable for clinical pharmacokinetic investigation of rosiglitazone maleate.