非洛地平和美托洛尔联用大鼠经皮给药的协同降压作用

Synergetic antihypertensive effect of transdermal administration of felodipine-metoprolol combination in rats

目的:研究非洛地平和美托洛尔联用经皮给药对自发性高血压大鼠的协同降压作用,为其复方经皮给药系统的研制提供药理学依据。方法:50只自发性高血压大鼠随机分为10组(均为单次给药):空白对照组,非洛地平-美托洛尔剂量分别为1-10、3-30、9-90 mg/kg的复方透皮贴剂治疗组,非洛地平剂量分别为1、3、9 mg/kg和美托洛尔剂量分别为10、30、90 mg/kg的单方透皮贴剂治疗组。以无创性尾套法测定给药后大鼠的血压和心率,评价两药联用的协同降压作用。结果:非洛地平和美托洛尔联用经皮给药对收缩压和舒张压的降低作用均显著高于两药各自单用(P<0.05),对心率有降低作用但显著低于单用美托洛尔(P<0.05)。单方与复方药物经皮给药对血压及心率的作用强度和持续时间均具有剂量依赖性(P<0.05)。结论:作用机制不同的非洛地平和美托洛尔联用,协同和互补作用明确,该透皮给药复方制剂可以提高血压控制率、治疗安全性和病人用药依从性。

Objective：To study the synergetic antihypertensive effect of transdermal drug delivery system（TDDS） of felodipine and metoprolol on spontaneously hypertensive rats（SHR）. Methods： Fifty SHR were divided into 10 groups and they were treated with a single dose of placebo,transdermal patch containing felodipine-metoprolol 1-10, 3-30, 9-90 mg/kg, transdermal patch containing felodipine 1, 3, 9 mg/kg, and transdermal patch containing metoprolol 10, 30, 90 mg/kg, respectively. Harmless tail-cuff method was used to determine blood pressure and heart rate of the rats. The synergetie antihypertensive effect of felodipine and metoprolol was evaluated. Results： The antihypertensive efficacy of transdermal administration of felodipine and metoprolol in combination was significantly better（P〈0.05） than that of each drug alone, but the reduction in heart rate was significantly less than that of metoprolol （P〈0.05）. Both single and compound preparations possessed significantly dose-dependent antihypertensive effects（P〈0.05）. Conclusion： Felodipine and metoprolol lower blood pressure via different but complementary mechanisms and synergetic antihypertensive effect of them is definite. This compound preparation can improve antihypertensive efficacy,therapeutic safety and compliance of patients.