Tripathi A S, Mazumder P M, Chandewar A V
Department of Pharmacology, P. Wadhwani College of Pharmacy, Yavatmal, Maharashtra, India.
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
Exp Clin Endocrinol Diabetes. 2014 Nov;122(10):597-601. doi: 10.1055/s-0034-1382034. Epub 2014 Jul 8.
The present study investigate the drug interaction of Glimepiride (GLIM) with Sildenafil Citrate (SIL) in Diabetic Nephropathy (DN) rats. Diabetes was induced in rats by administering Streptozotacin i. e. STZ (60 mg/kg). In present investigation GLIM (0.5 mg/kg, P.O.) and SIL (2.5 mg/kg, P.O.) were given for 6 weeks after the confirmation of DN. Pharmacodynamic and kinetic parameters were estimated after 1(st) dose and at the end of 6(th) week of drug administration. There was significant (p<0.001) increase in the bioavailability of GLIM in the presence of SIL in DN after the 1(st) dose of administration of the drug as compared to GLIM treated rat, whereas at the end of 6(th) week of drug administration, there were significant (p<0.0001) decrease in the bioavailability of GLIM+SIL treated DN rats compared to GLIM treated rats. There was significant (P<0.01) reduction of blood glucose level in GLIM+SIL treated group as compare to only GLIM treated group on 1(st) dose of drug administration but after continuous treatment for next 6 weeks, GLIM treated group showed significant hypoglycemia which was found to be reduced in GLIM+SIL treated group significantly. The present study concluded that GLIM+SIL treatment reduces the hypoglycemic condition which was there for GLIM treated DN rat.
本研究调查了格列美脲(GLIM)与枸橼酸西地那非(SIL)在糖尿病肾病(DN)大鼠中的药物相互作用。通过腹腔注射链脲佐菌素(STZ,60mg/kg)诱导大鼠患糖尿病。在本研究中,在确认患有DN后,给予GLIM(0.5mg/kg,口服)和SIL(2.5mg/kg,口服)6周。在给药第1剂后以及给药6周结束时评估药效学和动力学参数。与仅用GLIM治疗的大鼠相比,在给药第1剂后,在患有DN且同时存在SIL的情况下,GLIM的生物利用度显著增加(p<0.001);而在给药6周结束时,与GLIM治疗的大鼠相比,GLIM+SIL治疗的DN大鼠的生物利用度显著降低(p<0.0001)。在给药第1剂时,与仅用GLIM治疗的组相比,GLIM+SIL治疗组的血糖水平显著降低(P<0.01),但在接下来连续治疗6周后,GLIM治疗组出现显著低血糖,而GLIM+SIL治疗组的低血糖情况显著减轻。本研究得出结论,GLIM+SIL治疗可减轻GLIM治疗的DN大鼠所出现的低血糖状况。