Interactions of Metoclopramide and Ciprofloxacin on Electrocardiographic Indices in Anesthetized Normal and Hyperthermic Rats

BACKGROUND: The combination of metoclopramide (MCP) and ciprofloxacin (CPX) is not uncommon in clinical practice, as nausea and vomiting are well known during febrile illness. Some reports in the literature have linked both MCP and CPX to serious cardiac adverse effects including QT prolongation and cardiac arrests. In this study we examined the effect of the combination between MCP and CPX on the ECG parameters and serum potassium in normothermic and hyperthermic rats. METHODS: Thiopental-anesthetized rats were injected i.v. with MCP (0.2 mg/kg) and/or CPX (20 mglkg) after induction of hyperthermia by intracerebroventricular administration of PGEz (0.4 flglkg). ECG recordings were done every 10 min during 90-min duration. Plasma potassium was measured at 0, 20, 40, 60, and SO-min. RESULTS: small doses of MCP and CPX changed ECG indices in statistically significant manner at normal and elevated body temperatures. MCP produced early bradycardia and prolongation of PR interval although it was less pronounced during hyperthermia possibly due to increased sympathetic nerve discharge. It also produced slight increase in QT interval (-4 ms) in normo- and hyperthermia. On the other hand, CPX caused non-significant effects on HR and conduction velocity but prolonged the QT interval by -4.3 ms during normo- and hyperthermia. Combination of MCP and CPX did not affect the influence of MCP alone on the HR or conduction velocity while it exaggerated their individual effects on the QT and QTc prolongation. This interaction was not affected by hyperthermia. CONCLUSION: the combination of MCP and CPX should be avoided as it may lead to serious QT prolongation while hyperthermia is not considered a dangerous threat for this interaction.