Aim: The present study was designed to evaluate the pharmacodynamic drug-drug interaction between enalapril and concomitantly administered diclofenac sodium in osteoarthritic hypertensive [with or without type 2 diabetes mellitus (T2DM)] patients.

Materials and Methods: Total of 67 patients were randomized to either only enalapril 10 mg or concomitant treatment of enalapril 10 mg and diclofenac sodium 100 mg for 8-12 weeks in diseased states of hypertension and osteoarthritis with or without T2DM. Patients were assessed for systolic BP (SBP), diastolic BP (DBP), insulin sensitivity, urinary albumin excretion rate (UAER), serum sodium (S. Na⁺), serum potassium (S. K⁺), serum creatinine (S_cr), creatinine clearance (CLCR) and blood urea nitrogen (BUN).        

Results and Discussion: Baseline demographics and characteristics of the patients were comparable amongst all the groups. Adequately controlled antihypertensive effect of enalapril was significantly attenuated by diclofenac sodium when concomitantly administered with enalapril among diabetic (SBP: p=0.004; DBP: p=0.007) and non-diabetic (SBP: p=0.007; DBP: p=0.00006) pool of the patients. Insulin sensitivity was improved (p=0.001) and UAER (p=0.04) was better controlled among enalapril treated diabetic patients, while these effects were attenuated in diabetic patients receiving enalapril and diclofenac sodium concomitantly. Serum Na⁺ and S. K⁺ levels were reduced and raised significantly in diabetic (S. Na⁺: p=0.02; S. K⁺: p=0.002) as well as and non-diabetic (S. Na⁺: p=0.013; S. K⁺: p=0.03) patients, respectively. In non-diabetic pool, S_cr, CLCR and BUN were significantly increased (p=0.002), lowered (p<0.000001) and raised (p=0.006), respectively, with enalapril and diclofenac sodium concomitant treatment. BUN was significantly increased (p=0.014).               

Conclusion: With the attenuation of antihypertensive efficacy, the chronic concomitant treatment of oral diclofenac sodium with enalapril leads to deterioration of insulin sensitivity (in T2DM patients), serum electrolytes and renal function in osteoarthritic hypertensive patients (with or without T2DM).

Keywords: diclofenac sodium; hypertension; enalapril, osteoarthritis, type-2 diabetes mellitus.

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Dr Sunita Goswami, M.Pharm PhD

Associate Professor, Department of Pharmacology, L.M. College of Pharmacy, Navarangpura, Amedabad-380009, Gujarat, INDIA