氨氯地平与比索洛尔在Beagle犬体内的药动学相互作用研究

目的探讨氨氯地平与比索洛尔联合用药时有无显著的药动学相互作用。方法采用自身对照、随机交叉试验方法,将Beagle犬分成3组,每组2条,分别按试验周期服用氨氯地平对照药物、比索洛尔对照药物以及氨氯地平与比索洛尔复方药物。采用HPLC-UV和HPLC-FLD分别测定不同时间点氨氯地平与比索洛尔的血药质量浓度,计算药动学参数。结果氨氯地平单用时ρmax为(110.2±6.3)μg.L-1,AUC0-∞为(1 984±594)μg.h.L-1;联合用药时ρmax为(102.0±23.5)μg.L-1,AUC0-∞为(2 016±394)μg.h.L-1。比索洛尔单用时ρmax为(35.77±8.17)μg.L-1,AUC0-∞为(230.2±93.9)μg.h.L-1;联合用药时ρmax为(31.74±7.57)μg.L-1,AUC0-∞为(224.8±106.1)μg.h.L-1。故与两种药物单独使用相比,联合用药时的ρmax、AUC差异没有统计学意义。结论氨氯地平与比索洛尔联合用药不存在显著的药动学相互作用。

Pharmacokinetics interaction study between amlodipine and bisoprolol in Beagle dogs

Objective To investigate whether there is pharmacokinetic interaction between amlodipine and bisoprolol when administered jointly into Beagle dogs. Methods Six healthy adult beagle dogs were evenly divided into 3 groups according to a self-controlled randomized 2-way crossover design. The 3 groups were orally given amlodipine powder, bisoprolol powder or compound powder of amlodipine and bisoprolol, respectively. The concentrations of amlodipine and bisoprolol in Beagle dog plasma were determined respectively at specified time points by HPLC-UV and HPLC-FLD method; the pharmacokinetic parameters were calculated subsequently. Results ρ_max and AUC_0-∞were (110.2 ± 6.3) μg·L^-1 and (1 984 ± 594) μg·h·L^-1 when administered amlodipine alone and those were (102.0 ± 23.5) μg·L^-1 and (2 016 ± 394) μg·h·L^-1 when combined amlodipine with bisoprolol, respectively. ρ_max and AUC_0-∞were (35.77 ± 8.17) μg·L^-1 and (230.2 ± 93.9) μg·h·L^-1 when administered bisoprolol alone and those were (31.74 ± 7.57) μg·L^-1 and (224.8 ± 106.1) μg·h·L^-1 when combined bisoprolol with amlodipine, respectively. There were no significant differences in ρ_max and AUC_0-∞ of the two drugs when they were used alone or jointly. Conclusion There is no obvious pharmacokinetic interaction between amlodipine and bisoprolol when they are administered jointly into Beagle dogs.