Document Type : Original Article(s)


1 Assistant Professor, Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

2 Department of Orthopedic Surgery, Tehran University of Medical Sciences, Tehran, Iran

3 Department of General Surgery, Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Medical Physics and Radiology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

5 Assistant Professor, Department of Cardiology, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

6 Department of Internal Medicine, Razavi Hospital, Imam Reza International University, Mashhad, Iran

7 Department of Extra-Corporeal Circulation, Razavi Hospital, Imam Reza International University, Mashhad, Iran


BACKGROUND: Digoxin is a drug for ventricular rate control in atrial fibrillation (AF). The major challenge in digoxin therapy is to adjust the appropriate concentration range for this drug due to its narrow therapeutic index. Unique physiochemical properties of drinking water affect the pharmacological actions and delivery of drugs to the body whether they are administered orally, topically, or by injection. The aim of this study was to evaluate water hardness effect on digoxin therapy in an experimental rat model.METHODS: 48 rats weighing 200-220 g were randomly assigned to three groups that received drinking water with 50, 400, and 800 mg/l hardness degrees for 28 days. Then each group was assigned into two groups. One received digoxin 0.2 mg/kg a day orally for four days. The other group received normal saline (as control group). Continuous recording of electrocardiogram (ECG) was performed by PowerLab system (AD Instruments Company) before and day 4 of digoxin treatment. Then serum samples were collected and assessed for digoxin, sodium, potassium, calcium, magnesium, blood urea nitrogen (BUN), and creatinine levels.RESULTS: Water hardness in the range of 50-800 mg/l had no effect on serum digoxin levels (P > 0.050), but consuming hard drinking water (400 and 800 mg/l) could increase serum calcium levels and then cause mortality (37.5% in both groups), following changes in ECG due to digoxin consumption.CONCLUSION: Consuming hard drinking water probably interferes with digoxin pharmacodynamics in the way of toxicity induction.


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