期刊
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
卷 33, 期 1, 页码 3-10出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/JCP.0b013e31827c0314
关键词
QT study; iloperidone; QTcF; atypical; antipsychotic; pharmacogenetics; drug-drug interaction
资金
- Novartis Pharmaceuticals Corporation
- Baxter
- Bioline
- Bristol-Myers Squibb
- Cephalon, Inc
- Cortex
- Eisai, Inc
- Eli Lilly
- Forest Laboratories
- Genentech
- Janssen Pharmaceutical
- Lundbeck
- Merck
- Novartis
- Organon
- Otsuka
- Pfizer Wyeth
- Shire Development
- Solvay Pharmaceuticals
- Sunovion
- Roche
- Takeda Pharmaceuticals International
- Takeda Global Research and Development
- NIAAA
- NIBIB
- NIH/NCRR
- University of Southern California
- University of California San Francisco
- University of California San Diego
- Baylor College of Medicine
- American Psychiatric Association
- Alzheimer's Association
- Abbott
- Allergan
- Biovail
- Boehringer Ingelheim
- Eisai
- Evotec
- Ipsen
- Johnson Johnson
- Labopharma
- Link Medicine
- NovaDel Pharma
- Orexigen
- Prexa
- Psyllin
- Pfizer
- Takeda
- Targacept
The potential for iloperidone, a D2/5-HT2A antipsychotic, to affect the heart rateYcorrected QT interval (QTc) was assessed in the absence and presence of metabolic inhibitors in a randomized, open-label, multicenter study. QTinterval prolongation by medications, including both conventional and atypical antipsychotic drugs, can predispose patients to cardiac arrhythmias and result in sudden death. Adults with schizophrenia or schizoaffective disorder and normal electrocardiograms at baseline (N = 188) were randomized 1: 1: 1: 1: 1 to iloperidone, 8 mg twice daily (BID), 12 mg BID, 24 mg once daily (QD); quetiapine, 375 mg BID; or ziprasidone, 80 mg BID during period 1 (no metabolic inhibitors present). Iloperidone BID produced mean changes in QTc Fridericia correction (QTcF) interval (8.5-9.0 milliseconds [ms]) similar to those produced by ziprasidone (9.6 ms) and higher than those produced by quetiapine (1.3 ms). Iloperidone, 24 mg QD, produced a mean QTcF change of 15.4 ms. Coadministration of metabolic inhibitors with iloperidone during periods 2 (paroxetine) and 3 (paroxetine and ketoconazole) resulted in greater increases in the QTc interval. Increased QTc was observed in individuals with specific cytochrome P450 2D6 polymorphisms. Up to 10% of patients on iloperidone experienced QTc intervals of 60 ms or longer in the presence of metabolic inhibition and QD dosing. However, no patients experienced QTc changes of clinical concern (QTc >= 500 ms). The most common adverse events with iloperidone were headache, anxiety, and dyspepsia. The only cardiovascular adverse events with iloperidone were non-concentration-dependent tachycardia that was mild in most patients and did not lead to further sequelae. Pharmacogenetics and recommendations are discussed.
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