Abstract：
:Since an antipsychotic drug haloperidol has been clinically reported to induce QT interval prolongation and torsade de pointes, in this study its risk stratification for the onset of torsade de pointes was performed by using the chronic atrioventricular block canine model with a Holter electrocardiogram. Haloperidol in a dose of 3 mg kg-1 p.o. prolonged the QT interval, but it did not induce torsade de pointes during the observation period of 21 h (n = 4), indicating that the dose would be safe. Meanwhile, haloperidol in a dose of 30 mg kg-1 p.o. significantly increased the short-term variability in beat-to-beat analysis of QT interval (n = 4), and it induced torsade de pointes in 4 animals out of 4, showing that the dose could be torsadogenic. Since 3 mg kg-1 p.o. of haloperidol in this study can be estimated to provide about 8 times higher plasma concentrations than its therapeutic level, haloperidol may be used safely for most of the patients, as long as its plasma drug concentration is kept within the therapeutic range.
journal_name
Cardiovasc Toxicoljournal_title
Cardiovascular toxicologyauthors
Izumi-Nakaseko H,Nakamura Y,Cao X,Wada T,Ando K,Sugiyama Adoi
10.1007/s12012-016-9388-5subject
Has Abstractpub_date
2017-07-01 00:00:00pages
319-325issue
3eissn
1530-7905issn
1559-0259pii
10.1007/s12012-016-9388-5journal_volume
17pub_type
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