title: Hypokalemia: a potent risk for QTc prolongation in clarithromycin treated rats.
abstract: Clarithromycin belongs to macrolide group of antibiotics commonly known for their proarrhythmic potency. Besides agents interfering with CYP 3A, electrolyte imbalance might influence repolarization problems of clarithromycin. The proarrhythmic tendency of clarithromycin particularly in association with hypokalemia manifested a change in QT interval in rat electrocardiogram (ECG). Varying degree of hypokalemia was induced by intraperitoneal injection of furosemide (50, 30, and 10 mg/kg, for seven days). The serum electrolyte levels confirmed that hypokalemia was established in the groups receiving furosemide. Simultaneously, clarithromycin was orally administered in the doses of 100 and 80 mg/kg for seven days. ECG was measured for 5 min in anaesthetised rat before and after 2 h of treatment. The QT interval was corrected for heart rate and reported as corrected QT (QTc). Distinct QTc interval prolongation was observed in groups receiving furosemide (50 and 30 mg/kg) alone and in all the groups receiving clarithromycin alongside furosemide. Neither, clarithromycin (80 mg/kg) nor furosemide (10 mg/kg) exhibited any significant change in the QTc interval but in combination these drugs led to a significant increase in the QTc interval. Most interestingly, potassium supplementation was found to reduce QTc interval in the group presenting with maximum QTc prolongation. These results suggest that hypokalemic condition potentiates the clarithromycin induced QTc prolongation, thereby indicating the importance of monitoring serum electrolyte during clarithromycin therapy. Although, selection of rat for examination of proarrhythmic liability is controversial, this report may be considered as an evidence of hypokalemia potentiating clarithromycin induced QTc prolongation.
authors.affiliation: Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. sanmoykarmakar@gmail.com
authors.forename: Sanmoy
authors.initials: S
authors.lastname: Karmakar
authors.forename: Aswathi
authors.initials: A
authors.lastname: Padman
authors.forename: Naga
authors.initials: N
authors.lastname: Swamy Mane
authors.forename: Tuhinadri
authors.initials: T
authors.lastname: Sen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004573:Electrolytes / Q000097:blood; D005665:Furosemide; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007008:Hypokalemia / Q000097:blood / Q000178:diet therapy / Q000503:physiopathology*; D008297:Male; D017419:Potassium, Dietary / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D012720:Severity of Illness Index; D013535:Suspensions
chemical_list: D000900:Anti-Bacterial Agents; D004573:Electrolytes; D017419:Potassium, Dietary; D013535:Suspensions; D005665:Furosemide; D017291:Clarithromycin