Background: The present study was designed as an open label, multiple-dose, randomized, parallel trial to evaluate the pharmacodynamic drug-drug interaction of lisinopril and concomitantly administered diclofenac sodium in non-diabetic and diabetic, mild to moderate hypertensive, osteoarthritic patients.
Methods: Post-screening and on inclusion, patients were put on a 2-week washout period and then randomly assigned to either only lisinopril 10 mg or combination of lisinopril 10 mg and diclofenac sodium 100 mg treatments for 8-12 weeks in diseased states of hypertension and osteoarthritis with or without type 2 diabetes mellitus.
Results: The blood pressure (BP) control with lisinopril was reduced by concomitantly administered diclofenac sodium in non-diabetic (SBP: p=0.00002; DBP: p=0.000008) and diabetic (SBP: p=0.002; DBP: p=0.001) patients when compared with the patients receiving lisinopril alone. Insulin sensitivity was improved (p=0.00002) and urinary albumin excretion rate was better controlled (p=0.0096) in lisinopril-treated patients when compared with the combination treatment in diabetic pool. Serum creatinine levels increased significantly in non-diabetic patients (p=0.00004) receiving combination treatment. In addition, creatinine clearance (CLCR) and blood urea nitrogen (BUN) were significantly higher in diabetic (CLCR: p<0.00001; BUN: p=0.0098) as well as in non-diabetic (CLCR: p<0.00001; BUN: p=0.03) patients treated with combination treatment. The alterations in serum electrolytes, reduction in % platelet aggregation activity and improvement in lipid profile was more profound with combination treatment in comparison to lisinopril alone.
Conclusions: The antihypertensive efficacy and insulin sensitivity improving property of lisinopril along with the renal function might get worse in hypertensive osteoarthritic patients receiving concomitant treatment of oral diclofenac sodium with lisinopril. In addition to this, close monitoring of serum electrolytes is also suggested to rule out any long-term detrimental effect.