Toxic Effects of Trastuzumab (Herceptin) Combined with Doxorubicin in Chick Embryos

Yuji Yoshiyama1, Takashi Sugiyama2 and Motoko Kanke1
1 Kyoritsu College of Pharmacy, 2 Kitasato University

Correspondence: Yuji Yoshiyama, Ph.D.
Division of Clinical Pharmacy, Kyoritsu College of Pharmacy
1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan
Tel 03-5400-2667, Fax 03-5400-2667,

Original paper :AATEX 9(2-3):40-44
The toxic activity of trastuzumab combined with doxorubicin was studied in chick embryos. Fertilized eggs of White Leghorns were incubated and used for experiment. Trastuzumab was injected with and without doxorubicin into the air sac of fertilized eggs. Electrocardiograms were recorded 0 to 60 min after the injection. After injection of each drug alone, the heart rate was not different compared with non-injected control. However, the heart rate was significantly decreased by injection with a combination of trastuzumab with doxorubicin. In addition, arrhythmia was produced by injection of both trastuzumab and doxorubicin. These findings indicate that the combination of trastuzumab with doxorubicin has a marked influence on the heart rate in chick embryos.

Key words: toxic interaction, trastuzumab, doxorubicin, chick embryo, electrocardiogram