IMPACT OF ANTI-HYPERTENSIVE AGENT ON ANTI-DIABETIC DRUG IN DIABETIC AND NON-DIABETIC RATS – ASSESSMENT OF DRUG–DRUG INTERACTIONS

ANAND ARUMUGAM; VENKATA RAJESHAM V

doi:10.22159/ajpcr.2025v18i3.53818

Authors

ANAND ARUMUGAM Department of Pharmacology, Bir Tikendrajit University, Canchipur, Manipur, India.
VENKATA RAJESHAM V Department of Pharmacology, Bir Tikendrajit University, Canchipur, Manipur, India. https://orcid.org/0009-0008-5341-1934

DOI:

https://doi.org/10.22159/ajpcr.2025v18i3.53818

Keywords:

Captopril, Metformin, Drug interactions, Pharmacokinetic and pharmacodynamic interaction

Abstract

Objectives: The investigation was planned to evaluate pharmacokinetic and pharmacodynamic drug communication of Captopril and Metformin in healthy and diabetic albino Wistar rats succeeding single and many dosage treatments.

Methods: Therapeutic doses of captopril and metformin were administered to animal models, blood glucose levels were assessed by glucose oxidase-peroxidase (GOD-POD) method technique, and plasma captopril and metformin amounts were estimated by reversed-phase high-performance liquid chromatography (HPLC) technique to compute the pharmacokinetic attributes. In the present work, the pharmacokinetic and pharmacodynamic interaction between captopril and metformin was evaluated. Pre-clinical investigation might be supportive of evading drug–drug interactions in medical conditions. By means of HPLC, concentration versus time data were plotted for direct extraction of the pharmacokinetic attributes, peak plasma concentrations (Cmax), and time to reach peak concentration (tmax). The linear trapezoidal rule was used in this work to compute AUC from 0 h to 24 h, which is denoted by AUC 0-t.

Results: In the determination of fasting serum glucose concentration in normal and streptozotocin-inducted diabetic animals on day 1 and day 8, there was a tremendous decline in the glucose levels in a significant manner (**p<0.001). When captopril alone administered group was compared to the group in combination with metformin on days 1 and 8, there was no significant variance in Cmax, Tmax, AUCo-t, and AUCo-inf.

Conclusion: The results concluded from the kinetic analysis revealed that there were no significant interactions in the kinetic parameters of metformin and captopril, both alone and in combination. However, further possible investigations are needed which might be helpful for diabetes.

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References

Karalliedde J, Gnudi L. Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease. Nephrol Dial Transplant. 2016;31(2):206-13. doi: 10.1093/ndt/gfu405, PMID: 25550448

Adeloye D, Ige JO, Aderemi AV, Adeleye N, Amoo EO, Auta A, et al. Estimating the prevalence, hospitalisation and mortality from type 2 diabetes mellitus in Nigeria: A systematic review and meta-analysis. BMJ Open. 2017;7(5):e015424. doi: 10.1136/bmjopen-2016-015424, PMID: 28495817

Enhörning S, Melander O. The vasopressin system in the risk of diabetes and cardiorenal disease, and hydration as a potential lifestyle intervention. Ann Nutr Metab. 2018;72(Suppl 2):21-7. doi: 10.1159/000488304, PMID: 29925066

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. doi: 10.1016/j.diabres.2019.107843, PMID: 31518657

Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. 2016 Sep;24(5):547-53. doi: 10.1016/j. jsps.2015.03.013, PMID: 27752226, PMCID: PMC5059829

Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition. 2002;18(10):872-9. doi: 10.1016/s0899-9007(02)00916-4, PMID: 12361782

Khan MA, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes-global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10(1):107-11. doi: 10.2991/ jegh.k.191028.001, PMID: 32175717

Agofure O, Odjimogho S, Okandeji-Barry OR, Efegbere HA, Nathan HT. Pattern of diabetes mellitus-related complications and mortality rate: Implications for diabetes care in a low-resource setting. Sahel Med J. 2020;23(4):206-10. doi: 10.4103/smj.smj_64_19

Richens A. Pharmacokinetic and pharmacodynamic drug interactions during treatment with vigabatrin. Acta Neurol Scand Suppl. 1995;162:43- 6. doi: 10.1111/j.1600-0404.1995.tb00500.x, PMID: 7495190

Sun L, Mi K, Hou Y, Hui T, Zhang L, Tao Y, et al. Pharmacokinetic and pharmacodynamic drug-drug interactions: Research methods and applications. Metabolites. 2023 Jul 29;13(8):897. doi: 10.3390/ metabo13080897, PMID: 37623842, PMCID: PMC10456269

Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015 Oct 10;6(13):1246-58. doi: 10.4239/wjd.v6.i13.1246, PMID: 26468341, PMCID: PMC4600176

Ferrari R. RAAS inhibition and mortality in hypertension. Glob Cardiol Sci Pract. 2013 Nov 1;2013(3):269-78. doi: 10.5339/gcsp.2013.34, PMID: 24689028, PMCID: PMC3963752.

Cordonnier DJ, Zaoui P, Halimi S. Role of ACE inhibitors in patients with diabetes mellitus. Drugs. 2001;61(13):1883-92. doi: 10.2165/00003495-200161130-00001, PMID: 11708761

Hypertension in diabetes Study IV. Therapeutic requirements to maintain tight blood pressure control. Diabetologia. 1996 Dec;39(12):1554- 61. doi: 10.1007/s001250050614. Erratum in: Diabetologia. 1997 Mar;40(3):366. PMID: 8960842

Ghasemi A, Jeddi S. Streptozotocin as a tool for induction of rat models of diabetes: A practical guide. Excli J. 2023 Feb 21;22:274-94. doi: 10.17179/excli2022-5720, PMID: 36998708, PMCID: PMC10043433

Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother. 2010 Jul;1(2):87-93. doi: 10.4103/0976-500X.72350. Erratum in: J Pharmacol Pharmacother. 2017 Jul-Sep;8(3):153. doi: 10.4103/0976- 500X.215702, PMID: 29081629, PMCID: PMC3043327

Lindstrom NM, Moore DM, Zimmerman K, Smith SA. Hematologic assessment in pet rats, mice, hamsters, and gerbils: Blood sample collection and blood cell identification. Clin Lab Med. 2015 Sep;35(3):629-40. doi: 10.1016/j.cll.2015.05.011, PMID: 26297409

Govindarajan R, Tejas V, Pushpangadan P. High-performance liquid chromatography (HPLC) as a tool for standardization of complex herbal drugs. J AOAC Int. 2019 Jul 1;102(4):986-92. doi: 10.5740/ jaoacint.18-0378, PMID: 30558698

Shailajan S, Patil Y, Joshi M, Menon S, Mhatre M. Simultaneous quantification of pharmacological markers quercetin and berberine using high-performance thin-layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC) from a polyherbal formulation Pushyanuga churna. J AOAC Int. 2019 Jul 1;102(4):1003-13. doi: 10.5740/jaoacint.18-0380, PMID: 30563588

Kesarwani K, Gupta R, Mukerjee A. Bioavailability enhancers of herbal origin: An overview. Asian Pac J Trop Biomed. 2013 Apr;3(4):253- 66. doi: 10.1016/S2221-1691(13)60060-X, PMID: 23620848, PMCID: PMC3634921

Czigle S, Nagy M, Mladěnka P, Tóth J, OEMONOM. Pharmacokinetic and pharmacodynamic herb-drug interactions-part I. Herbal medicines of the central nervous system. PeerJ. 2023 Nov 15;11:e16149. doi: 10.7717/peerj.16149, PMID: 38025741, PMCID: PMC10656908

Simon Lati M, Gitonga David N, Njoki Kinuthia R. Clinical significance of potential drug-drug interactions and their targets for minimization among hypertensive diabetic outpatients at a Kenyan Referral Hospital. Int J Pharm Pharm Sci. 2020;12(10):6-11.

De Boer IH, Bangalore S, Benetos A, Davis AM, Michos ED, Muntner P, et al. Diabetes and hypertension: A position statement by the American Diabetes Association. Diabetes Care. 2017;40(9):1273-84. doi: 10.2337/dci17-0026, PMID: 28830958

Mitra SK, Sundaram R, Venkataranganna MV, Gopumadhavan S. Pharmacokinetic interaction of Diabecon (D-400) with rifampicin and nifedipine. Eur J Drug Metab Pharmacokinet. 1999;24(1):79-82. doi: 10.1007/BF03190014, PMID: 10412895

Hayward RA, Reaven PD, Wiitala WL, Bahn GD, Reda DJ, Ge L, et al. Investigators Follow-up of glycaemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;372(23):2197-206. doi: 10.1056/NEJMoa1414266, PMID: 26039600

Erdmann E. Microalbuminuria as a marker of cardiovascular risk in patients with type 2 diabetes. Int J Cardiol. 2006 Feb 15;107(2):147-53. doi: 10.1016/j.ijcard.2005.03.053, PMID: 15975669

Triplitt C. Drug interactions of medications commonly used in diabetes. Diabetes Spectr. 2006 Oct 1;19(4):202-11. doi: 10.2337/ diaspect.19.4.202

Manikandan R, Sri Sai Sudha N, Logaraj M. Assessment of medication adherence among patients with hypertension and diabetes mellitus in urban field practice. Asian J Pharm Clin Res. 2018;11(4):130-2. doi: 10.22159/ajpcr.2018.v11i4.23236

Scheen AJ. Drug interactions of clinical importance with anti-hyperglycaemic agents: An update. Drug Saf. 2005 Jul;28(7):601-31. doi: 10.2165/00002018-200528070-00004