Toxic interactions between fluconazole and disopyramide in chick embryos

The present study evaluated the effect of fluconazole on the heart, as well as and the toxic interactions between fluconazole and disopyramide in chick embryos. Chick embryos have been widely used in pharmacologic and toxicologic experiments for evaluating drug action. Fertilized eggs of White Leghorns were incubated and investigated. Fluconazole 0.4 mg/egg, 0.8 mg/egg, 1.2 mg/egg alone or disopyramide 0.3 mg/egg alone was injected into the air sac of each fertilized egg. And fluconazole 0.4 mg/egg with disopyramide 0.3 mg/egg was injected into the air sac of each fertilized egg. Electrocardiograms (ECGs) were recorded 0 to 60 min after the drug injection, and heart rate was determined from ECG wave cycles. Changes in heart rate were expressed as mean-percent changes of the drug-treated groups to the matched control. After the administration of fluconazole 0.4 mg/egg alone, the heart rate did not differ compared with that of the controls. However, the heart rate was significantly decreased with the administration of fluconazole 0.8 mg/egg and 1.2 mg/egg. The heart rate was also significantly decreased by the administration of fluconazole 0.4 mg/egg together with disopyramide 0.3 mg/egg. In addition, an arrhythmia was produced by fluconazole and disopyramide. These findings indicate that the interaction between fluconazole and disopyramide has a marked influence on the heart rate in chick embryos.