Shahsavand Shabnam, Moshirfar Mohammad, Seyed-Sharifi Seyed Hassan, Younessi-Heravi Mohammad Amin, Ghasemi Reza, Valaei Morteza, Yaghubi Mohsen
Assistant Professor, Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Department of Orthopedic Surgery, Tehran University of Medical Sciences, Tehran, Iran.
ARYA Atheroscler. 2020 Sep;16(5):235-243. doi: 10.22122/arya.v16i5.2112.
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.
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.
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.
Consuming hard drinking water probably interferes with digoxin pharmacodynamics in the way of toxicity induction.
地高辛是一种用于控制心房颤动（AF）心室率的药物。由于其治疗指数狭窄，地高辛治疗的主要挑战是调整该药物的合适浓度范围。饮用水独特的物理化学性质会影响药物的药理作用以及药物进入人体的方式，无论药物是口服、局部给药还是注射给药。本研究的目的是在实验大鼠模型中评估水硬度对地高辛治疗的影响。
将48只体重200 - 220克的大鼠随机分为三组，分别饮用硬度为50、400和800毫克/升的饮用水，持续28天。然后每组再分为两组。一组每天口服0.2毫克/千克地高辛，共四天。另一组接受生理盐水（作为对照组）。在给予地高辛治疗前及治疗第4天，通过PowerLab系统（AD仪器公司）连续记录心电图（ECG）。然后收集血清样本，评估地高辛、钠、钾、钙、镁、血尿素氮（BUN）和肌酐水平。
50 - 800毫克/升范围内的水硬度对血清地高辛水平无影响（P > 0.050），但饮用硬水（400和800毫克/升）会使血清钙水平升高，进而导致死亡率增加（两组均为37.5%），同时饮用后心电图因地高辛出现变化。
饮用硬水可能通过诱导毒性的方式干扰地高辛的药效学。
