Possible Drug–Drug Interaction between Warfarin and Azithromycin in Infected Rats with Hypercoagulable State

Background: Warfarin is frequently used in clinical practice in the treatment of deep vein thrombosis and as a prophylactic agent against thromboembolism. Unfortunately, many medical, herbal, and dietary agents affect the anticoagulant activity of warfarin. Azithromycin is one of the most frequently used antimicrobial agents mainly in respiratory tract infections. This work was designed to assess the possible interaction between azithromycin on the anticoagulant activity of warfarin and the effect of warfarin on the antibacterial activity of azithromycin with subsequent readjustment of the dose of both drugs when they are coadministered. Methodology: The current study used 72 male adult albino rats weighing 200–250 g (3–4 months old) that were randomly subdivided equally into nine groups. Hypercoagulable state in rats was induced by a single intraperitoneal injection of ellagic acid at a dose of 10.5 mg/kg for 5 min before collection of blood samples. Anticoagulant activity of warfarin was assessed by prothrombin time (PT), bleeding time (BT), and clotting time (CT). The parameters for the antibacterial activity of azithromycin were the viable bacterial count, myeloperoxidase enzyme activity in the blood, neutrophil enumeration, and determination of serum C-reactive protein and serum tumor necrosis-α. Results: No significant differences were noted on PT, CT, and BT of hypercoagulable rats treated with azithromycin compared with hypercoagulable rats only. Moreover, azithromycin did not affect the anticoagulant activity of warfarin, and no significant change was noted in PT, CT, and BT between rats treated and not treated with azithromycin. The antibacterial activity of azithromycin had not been affected by warfarin. Furthermore, no significant differences were noted between infected and warfarin-treated rats only concerning antibacterial activity. Conclusion: Warfarin and azithromycin can be safely used together without cross-interaction between each other. Moreover, dose adjustment is not needed if both drugs are co-administered.