皮下埋植超长效氨氯地平制剂对自发性高血压大鼠血压及血药浓度的影响

Effect of super long-acting subcutaneous implantable sustained-release amlodipine preparation on blood pressure and drug concentration in spontaneously hypertensive rats

目的:探讨皮下埋植超长效缓释氨氯地平制剂对自发性高血压大鼠(spontaneously hypertensive rats,SHR)血压及血液中药物浓度的影响。方法:用高分子聚合物聚己内酯合成载体,加入氨氯地平原料药制成可皮下埋植的缓释降压制剂。将雄性SHR随机分成模型对照组、空白载体组、药物灌胃组、缓释降压组,每组8只;另取8只雄性WKY大鼠作为正常对照组。将空白载体、氨氯地平缓释制剂分别植入空白载体组及缓释降压组SHR的颈背部皮下,药物灌胃组SHR予以氨氯地平溶液(0.45 mg/kg)灌胃,正常对照组、模型对照组大鼠给予同体积蒸馏水灌胃。干预期间,定期测定各组大鼠尾动脉血压,采静脉血检测血浆药物浓度,共干预88 d。结果:从干预后第5天开始,氨氯地平药物灌胃组及缓释降压组SHR收缩压、舒张压及平均动脉压均低于模型对照组(P<0.01),与正常对照组WKY大鼠差异无统计学意义(P>0.05);与药物灌胃组比较,缓释降压组SHR收缩压、舒张压及平均动脉压差异无统计学意义(P>0.05)。缓释降压组SHR氨氯地平血药浓度于第3天开始达到稳定水平,一直维持到干预后第88天。结论:皮下埋植超长效氨氯地平缓释制剂,用药1次,即可平稳降低SHR血压达标维持88 d,且能维持稳定的血药浓度。

Objective:To investigate the effects of super long-acting subcutaneous implantable sustained-release amlodipine preparation on blood pressure and blood concentration of amlodipine in spontaneous hypertensive rats(SHR).Methods:The carrier was synthesized with high molecular polymer polycaprolactone,and amlodipine raw material was added to make a slow-release antihypertensive preparation that could be implanted subcutaneously.SHR was randomly divided into model control group,blank carrier group,drug gavage group,and sustained-release hypotension group,with 8 rats in each group.Another 8 male WKY rats were used as normal control group.The blank carrier and amlodipine sustained-release preparation were implanted under the skin of the neck and back of the blank carrier group and the sustained-release hypotension group,respectively.Amlodipine solution(0.45 mg/kg)was given to the SHR in the drug gavage group,and the rats in the normal control group and model control group were given the same volume of distilled water.During the intervention period,the rats′tail arterial blood pressure was measured and venous blood was collected to detect the blood drug concentration regularly,and corresponding intervention lasted for 88 days.Results:From the 5th day after intervention,systolic blood pressure,diastolic blood pressure and mean arterial pressure of SHR in drug gavage group and sustained-release hypotension group were lower than those of the model control group(P<0.01),and there was no statistical difference between the above groups and the normal control group(P>0.05).Compared with drug gavage group,there was no significant difference in SHR systolic blood pressure,diastolic blood pressure and mean arterial pressure in sustained-release hypotension group(P>0.05).Amlodipine concentration of SHR in sustained-release hypotension group reached a stable level on the 3rd day and remained until the 88th day after intervention.Conclusion:Subcutaneous implantation of super long-acting subcutaneous implantable sustained-release amlodipine preparation,with one dose,could steadily reduce SHR blood pressure standards for 88 days and maintain a stable blood concentration.