间-尼索地平Beagle犬静脉给药后体内药动学研究

 目的建立Beagle犬血浆中间-尼索地平RP-HPLC测定方法,研究Beagle犬静脉注射间-尼索地平后体内药动学。方法色谱条件:Waters C₁₈色谱柱(3.9 mm×300 mm,10μm);流动相:甲醇-水(64∶36);检测波长:236 nm;柱温:30℃;流速:1.0 mL·min^-1。Beagle犬静脉注射间-尼索地平后定时取血,用RP-HPLC测定血浆药物浓度,3P97软件计算药动学参数。结果间-尼索地平在1.875～480μg·L^-1内线性关系良好(r=0.999 9);Beagle犬静脉注射0.1,0.2,0.5 mg·kg^-1间-尼索地平后药动学行为均符合二室模型,AUC与剂量呈正相关,t_1/2α分别为6.32,7.07和16.0 min;t_1/2β分别为136,149和137 min;V_c分别为4.4,6.7和10.3 L;CL分别为0.20,0.20和0.30 L·min^-1。结论本方法操作简便,灵敏度高,稳定性好,可满足药动学研究需要。

Pharmacokinetics of m-Nisoldipine After an Intravenous Administration in Beagle dogs

OBJECTIVE To establish a reversed phase high performance liquid chromatographic(RP-HPLC) method for the measurement of m-nisoldipine(m-Nis) in the plasma of Beagle dogs and to investigate the pharmacokinetics of m-Nis after an intravenous administration in Beagle dogs.METHODS The analysis was performed on a Waters C₁₈ column(3.9 mm×300 mm, 10 μm)at 30 ℃ with the mobile phase of methanol-water(64∶36) at a flow rate of 1.0 mL·min^-1.The detect wavelength was at 236 nm.The plasma samples were collected after an intravenous administration of m-Nis in Beagle dogs.The plasma concentrations of m-Nis were measured using HPLC method and the pharmacokinetic parameters were calculated by 3P97.RESULTS The calibration curve of m-Nis was linear in the range of 1.875～480(μg·L^-1) with a correlation coefficient of 0.999 9.The plasma concentration-time curves of mNis were fitted with a two-compartment open pharmacokinetic model.The main pharmacokinetic parameters of m-Nis after a single dose of 0.1,0.2 and 0.5 mg·kg^-1of m-Nis in Beagle dogs were: t_1/2α 6.32,7.07 and 16.0 min;t_1/2β 136,149 and 137 min;V_c 4.4,6.7 and 10.3 L;CL 0.20,0.20 and 0.30 L·min^-1,respectively.CONCLUSION The method is sensitive,stable and easy to process.It is practical and suitable for the pharmacokinetic study of m-Nis.