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目的建立同时测定大鼠血浆中缬沙坦、硝苯地平的HPLC-UV分析方法,研究缬沙坦与硝苯地平联合应用后在大鼠体内是否存在药动学上的相互作用,为指导临床合理联合用药提供参考。方法选取18只雄性Wistar大鼠随机分成3组,分别为缬沙坦组(16 mg·kg~(-1))、硝苯地平组(4.2 mg·kg~(-1))和联合用药组(含缬沙坦16 mg·kg~(-1),硝苯地平4.2 mg·kg~(-1))。于给药前及给药后0.08、0.16、0.25、0.5、0.75、1、2、4、8、10、24 h由大鼠尾静脉采血,HPLC-UV测定缬沙坦和硝苯地平的血药浓度,通过非房室模型分析计算药动学参数。结果与缬沙坦组比较,联合用药组中缬沙坦的ρmax、AUC0-t显著增大(P<0.05),tmax显著缩短(P<0.05),CLz/F显著降低(P<0.05);与硝苯地平组比较,联合用药组中硝苯地平的t1/2z/h显著缩短(P<0.05),其他药动学参数无显著性差异。结论联合应用缬沙坦和硝苯地平可显著提高缬沙坦在大鼠体内的血药浓度和生物利用度,吸收入血加快,排泄减慢,而对硝苯地平除半衰期显著缩短外其他药动学参数无显著差异。
OBJECTIVE To establish a HPLC-UV method for the simultaneous determination of valsartan and nifedipine in rat plasma and to investigate the pharmacokinetic interaction between valsartan and nifedipine in rats. A reasonable combination of medication for reference. Methods Eighteen male Wistar rats were randomly divided into three groups: valsartan group (16 mg · kg -1), nifedipine group (4.2 mg · kg -1) and combination group (Including valsartan 16 mg · kg -1, nifedipine 4.2 mg · kg -1). Blood was collected from the tail vein of rats at 0.08, 0.16, 0.25, 0.5, 0.75, 1, 2, 4, 8, 10 and 24 h before and after administration, and the blood of valsartan and nifedipine Drug concentration, pharmacokinetic parameters were calculated by non-compartmental model analysis. Results Compared with valsartan group, the values of pmax and AUC0 - t in valsartan group were significantly increased (P <0.05), tmax was significantly reduced (P <0.05) and CLz / F was significantly decreased (P <0.05). Compared with nifedipine group, t1 / 2z / h of nifedipine in combination group was significantly shortened (P <0.05), and other pharmacokinetic parameters had no significant difference. Conclusions Combination of valsartan and nifedipine can significantly increase the plasma concentration and bioavailability of valsartan in rats, which can accelerate the blood intake and excretion of nosadipine, and reduce the half-life of nifedipine significantly. No significant difference in kinetic parameters.