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 action. 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 fertilized 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 significantly 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


(AATEX: Altern. Animal Test. EXperiment.: Alternatives to Animal Testing and EXperimentation)