Shortening of the QT Interval After Food Can Be Used to Demonstrate Assay Sensitivity in Thorough QT Studies
| Autor: | Alex H. Wong, A. John Camm, Georg Ferber, Jorg Taubel, Asif Naseem |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male QT interval Electrocardiography Young Adult Double-Blind Method Heart Rate Heart rate medicine Humans Pharmacology (medical) PR interval Breakfast Pharmacology Meal Cross-Over Studies medicine.diagnostic_test business.industry Fasting Assay sensitivity Crossover study Confidence interval Food Anesthesia Biological Assay Female business |
| Zdroj: | The Journal of Clinical Pharmacology. 52:1558-1565 |
| ISSN: | 0091-2700 |
| Popis: | The effect of food was investigated under conditions of a thorough QT (TQT) study and with confirmation of assay sensitivity by the use of a positive control (400 mg of moxi- floxacin). Fifty-five healthy subjects were randomized to treatment and a sequence of fasted and fed baseline elec- trocardiography days. Subjects received standard breakfast 30 to 10 minutes prior to dosing. Measurement of QT interval was performed automatically with subsequent manual onscreen overreading using electronic calipers. A profound increase in heart rate of 9.4 bpm was observed in the fed condition compared with the fasted condition at 1.5 hours after dose with a corresponding shortening of QT (27 mil- liseconds); (baseline data). When corrected, QTcF interval was shortened significantly with the maximal effect observed at 2 hours after dose of 8.2 (95% confidence interval, 6-10) milliseconds. A concurrent shortening of the PR interval with a maximum value of 5.6 milliseconds was also observed. The findings of this study demonstrate that food alters the QT-RR relationship and shortens QTc and PR for at least 4 hours after a carbohydrate-rich meal. The findings are of regulatory interest as this study shows that normal physio- logical causes can shorten QTc significantly and that it could be used as a method to demonstrate assay sensitivity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text