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QT interval correction for drug-induced changes in body temperature during integrated cardiovascular safety assessment in regulatory toxicology studies in dogs: A case study
- Source :
- Journal of Pharmacological and Toxicological Methods. 81:136-143
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Introduction Cardiovascular safety assessment requires accurate evaluation of QT interval, which depends on the length of the cardiac cycle and also on core body temperature (BT). Increases in QT interval duration have been shown to be associated with decreases in BT in dogs. Methods An example of altered QT interval duration associated with changes in body temperature observed during a 4-week regulatory toxicology study in dogs is presented. Four groups of Beagle dogs received the vehicle or test item once on Day 1, followed by a 4-week observation period. Electrocardiogram (ECG) parameters were continuously recorded on Days 1 and 26 by jacketed external telemetry (JET). Core body temperature (BT) was measured with a conventional rectal thermometer at appropriate time-points during the Day 1 recording period. Results Decreased BT was observed approximately 2 h after treatment on Day 1, along with increased QT interval duration corrected according to the Van de Water formula (QTcV), but the effect was no longer observed after correction for changes in BT [QTcVcT = QTcV − 14(37.5 − BT)] according to the Van der Linde formula. No significant changes in QTcV were reported at the end of the observation period, on Day 26. Discussion The present study demonstrates that core body (rectal) temperature can easily be monitored at appropriate time-points during JET recording in regulatory toxicology studies in dogs, in order to correct QT interval duration values for treatment-related changes in BT. The successful application of the Van der Linde formula to correct QTc prolongation for changes in BT was demonstrated.
- Subjects :
- QT interval
Male
Patch-Clamp Techniques
Long QT syndrome
Jacketed external telemetry
030204 cardiovascular system & hematology
Toxicology
Beagle
Body Temperature
Electrocardiography
03 medical and health sciences
Dogs
0302 clinical medicine
Heart Rate
Heart rate
Dog
Potassium Channel Blockers
medicine
Animals
Humans
Telemetry
Pharmacology
Core body temperature
Core (anatomy)
Cardiovascular safety
medicine.diagnostic_test
Cardiac cycle
business.industry
medicine.disease
Ether-A-Go-Go Potassium Channels
Electrocardiogram
Long QT Syndrome
HEK293 Cells
Anesthesia
Female
Safety
business
Algorithms
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10568719
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmacological and Toxicological Methods
- Accession number :
- edsair.doi.dedup.....21d2b9529a5e11b7f6a522ea554f243a
- Full Text :
- https://doi.org/10.1016/j.vascn.2016.04.008