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

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...

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Bibliographic Details
Published in:Journal of Pharmacological Sciences 2005, Vol.99(5), pp.513-522
Main Authors: Sasaki, Hiroyuki, Shimizu, Noritsugu, Suganami, Hideki, Yamamoto, Keiji
Format: Article
Language:English
Subjects:
Animals
Blood Pressure - drug effects
conscious dog
conscious monkey
Databases, Factual
dl-sotalol
Dogs
Electrocardiography
Haplorhini
Heart Rate - drug effects
inter-facility variability
Laboratories
Long QT Syndrome - chemically induced
Male
Models, Animal
QTc interval
Reproducibility of Results
Sotalol - pharmacology
Telemetry
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Summary: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
ISSN:1347-8613
1347-8648
DOI:10.1254/jphs.QT-B6