卡托普利和低剂量阿司匹林在犬体内的药动学相互作用研究

 目的观察卡托普利和低剂量阿司匹林在犬体内的药动学相互作用。方法采用6只雄性健康犬进行随机交叉试验, 对犬单用卡托普利(30 mg·kg^-1)、阿司匹林(1.5 mg·kg^-1)及合用两药时的主要药动学参数进行比较。分别采用反相高效液相色谱法测定犬血浆中卡托普利及水杨酸浓度,药-时数据应用3P87程序经计算机拟合处理。结果与单用时相比,合用阿司匹林后卡托普利的消除速率常数(Ke)显著增加,消除半衰期(t_1/2Ke)明显缩短,但血药浓度峰值(c_max)、血药浓度达峰时间(t_max)、药-时曲线下面积(AUC)无显著性差异。而阿司匹林单用及联用卡托普利时的药动学参数均无显著性差异。结论低剂量阿司匹林联用卡托普利明显影响卡托普利的有关药动学参数,而阿司匹林本身不受影响,是否诱导卡托普利相关的药酶代谢值得进一步研究。

Pharmacokinetics interaction of captopril and low-dosage aspirin in dog

OBJECTIVE To observe the pharmacokinetic interaction between captopril and low-dosage aspirin in dog.METHODS The main pharmacokinetic parameters of captopril(30 mg·kg^-1)、aspirin( 1.5 mg·kg^-1)and their combination were comparatively investigated in an open randomized crossover study. Drug concentration in plasma was assayed by RP-HPLC method. Concentration-time curves were simulated by 3P87 program.RESULTS Compared with the group treated with captopril alone, Ke increased significantly and t_1/2 decreased significantly in the group with combined treatment. There was no significant difference in c_max,t_max and AUC. No statistical significant difference was found in the pharmacokinetic parameters between the group treated with aspirin alone and in the group with combined treatment. CONCLUSIONS The results suggested that aspirin stimulated the activity of drug-metabolizing enzymes and produced pharmacokinetic interaction with captopril, which resulted in the differences in Ke, t_1/2Ke and AUC of captopril. However,there was no effect on aspirin itself.