间-尼索地平Beagle犬静脉给药后体内药动学研究

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

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（3．9mm×300mm．10μm）；流动相：甲醇-水（64：36）；检测渡长：236nm；柱温：30℃；流速：1．0mL·min^-1。Beagle犬静脉注射间-尼索地平后定时取血，用RP-HIJLC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=0．9999）；Beagle犬静脉注射0．1，0．2，0．5mg·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，t1／2α分别为6．32，7．07和16．0min；t1/2β分别为136，149和137min；Vc分别为4．4，6．7和10，3L；CL分别为0．20,0．20和0.30L·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。

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 invesligate 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 clogs. The plasma concentrations of m-Nis were measured using HPLC method and the pharmaeokinetic 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 m-Nis were fitted with a two-eompartment open pharmacokinetie 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： t1/2α 6.32,7.07 and 16.0 min,t1/2β 136,149 and 137 rain; Vc 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 pharmacokinetie study of mNis.