QT PRODACT: Inter-facility Variability in Electrocardiographic and Hemodynamic Parameters in Conscious Dogs and Monkeys

Journal of Pharmacological Sciences

Hiroyuki Sasaki²  Hideki Suganami²  Noritsugu Shimizu¹  Keiji Yamamoto² 

[1] Kobuchisawa Laboratories, Fuji Biomedix Co., Ltd., Japan;Japan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Japan

关键词: conscious dog;    conscious monkey;    QTc interval;    inter-facility variability;    dl-sotalol;   

DOI  :  10.1254/jphs.QT-B6

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(60)Cited-By(24)Supplementary materials(4)In safety pharmacology studies, the effect of a test compound on the electrocardiogram is routinely examined by using conscious dogs. However, the results may be widely variable. The monkey, on the other hand, has scarcely been used for such studies; and as yet, there have not been reported studies on monkeys conducted at several facilities with a standard protocol. In the present study, we examined inter-facility variabilities in electrocardiographic and hemodynamic parameters as described below. We analyzed the data from 8 facilities (9 test groups) on dogs and 5 facilities (7 test groups) on monkeys. This data was obtained from the studies employing the following standard protocol: dl-Sotalol or a vehicle (0.5 w/v% methylcellulose solution) was given to animals; and the PR interval, QRS duration, QT interval, heart rate, and mean blood pressure were determined time-sequentially before and after administration of the vehicle or dl-sotalol in each test group. dl-Sotalol produced a prolongation of the maximum mean QTcF interval in conscious dogs and QTcB interval in conscious monkeys by more than 10% in every test group. No difference in the corrected QT interval among the test groups was observed in dogs, but a difference was observed in monkeys. Supplementary material (Appendix): available only at http://dx.doi.org/10.1254/jphs.QT-B6

【 授权许可】

Unknown