Toxic Interactions between Miconazole and Disopyramide in Chick Embryos

Yuji Yoshiyama and Motoko Kanke

Division of Clinical Pharmacy, Kyoritsu University of Pharmacy, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan

AATEX 11(2):112-117, 2005

The toxic interactions between miconazole and disopyramide were studied in chick embryos. Chick embryos have been widely used in pharmacologic and toxicologic experiments for evaluating drug ac-tion. Fertilized eggs of White Leghorns were incubated and investigated. Miconazole 1 mg/egg, 5 mg/egg, 10 mg/egg alone or disopyramide 0.3 mg/egg alone was injected into the air sac of each fertil-ized egg. Miconazole 1 mg/egg with disopyramide 0.3 mg/egg was injected into the air sac of each fer-tilized egg. Electrocardiograms (ECGs) were recorded after the drug injection, and heart rate was de-termined 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 miconazole 1 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 miconazole 5 mg/egg and 10 mg/egg. The heart rate was also sig-nificantly decreased by the administration of miconazole 1 mg/egg together with disopyramide 0.3 mg/egg. In addition, an arrhythmia was produced by miconazole and disopyramide. These findings in-dicate that the interaction between miconazole and disopyramide has a marked influence on the heart rate in chick embryos.

Key words: toxic interaction, miconazole, disopyramide, chick embryo, electrocardiogram