Drug Interaction of Minoxidil and Himplasia with Oral Anti Diabetic Drug Sitagliptin in Diabetic Rats

Dhanapuram Akhila Banu, Gopi Mareedu, Vivek B, Velmurugan C
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Abstract

Aim and Objective: Sitagliptin is given as an oral antidiabetic drug to treat Diabetes Mellitus. Minoxidil and himplasia may be co-prescribed along with sitagliptin to treat hypertension and BPH respectively. As such no information is available regarding the interaction taking place between sitagliptin, minoxidil and himplasia. Hence the present work has been aimed to find out the interaction with among the above said drugs in rodent model, since such studies cannot be performed in humans. Methods: Studies were conducted in normal and alloxan induced diabetic rats with oral doses of 9mg/kg B.W of sitagliptin, 9mg/kg B.W of minoxidil and 54mg /k g of himplasia and their combinations with adequate washout periods in between the treatments. Blood samples were collected at regular time intervals in rats through retro orbital puncture. All the blood samples were analyzed for blood glucose by GOD/POD method in pharmacodynamic studies and the serum sitagliptin concentrations were estimated by UV Spectrophotometry. Serum insulin was estimated by chemiluminescence assay. Results: Sitagliptin showed hypoglycemic action in both normal and diabetic rats and the peak action was observed at 6 h. Hyperglycemia was observed with minoxidil at 1st hour, hypoglycemia was observed with himplasia at 4th hour and the combination of minoxidil and himplasia showed biphasic response in blood glucose levels. The same responses were observed even in combination with sitagliptin. The serum sitagliptin concentrations were not altered by the co-administration of drugs. Serum insulin levels were inhibited by administration of minoxidil and potentiated by himplasia and initial reduction followed by surge observed with combination of minoxidil and himplasia. The similar responses were observed when co-administered with sitagliptin. Conclusion: Thus it could be concluded that the combination of minoxidil and himplasia should be taken with care for clinical benefits in diabetic patients. However, further studies should be carried out in non rodent species and in clinical settings are warranted.
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米诺地尔、欣普拉西亚与口服抗糖尿病药物西格列汀对糖尿病大鼠的相互作用
目的与目的:西格列汀作为口服降糖药治疗糖尿病。米诺地尔和欣普拉西亚可与西格列汀合用分别治疗高血压和前列腺增生。因此,没有关于西格列汀、米诺地尔和欣普拉西亚之间相互作用的信息。因此,本研究的目的是在啮齿动物模型中找出上述药物之间的相互作用,因为此类研究无法在人体中进行。方法:采用西格列汀9mg/kg B.W、米诺地尔9mg/kg B.W、欣帕拉西亚54mg /kg的口服剂量,并在给药间隙给予足够的洗脱期,对正常和四氧嘧啶诱导的糖尿病大鼠进行研究。采用眶回穿刺法定期采集大鼠血液样本。药效学研究采用GOD/POD法测定血糖,紫外分光光度法测定血清西格列汀浓度。用化学发光法测定血清胰岛素。结果:西格列汀对正常大鼠和糖尿病大鼠均有降糖作用,6 h降糖作用达到峰值。米诺地尔给药1 h出现高血糖,米诺地尔给药4 h出现低血糖,米诺地尔与欣普拉西亚合用血糖呈双相反应。即使与西格列汀联合使用,也观察到相同的反应。血清西格列汀浓度未因联合用药而改变。米诺地尔可抑制血清胰岛素水平,而米诺地尔和米诺地尔联合使用后,胰岛素水平开始下降,随后升高。当与西格列汀联合使用时,观察到类似的反应。结论:糖尿病患者应谨慎使用米诺地尔与欣帕拉西亚合用,以获得临床疗效。然而,进一步的研究应该在非啮齿动物物种和临床环境中进行。
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