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Raltegravir Thorough QT/QTc Study: A Single Supratherapeutic Dose of Raltegravir Does Not Prolong the QTcF Interval
Author(s) -
Iwamoto M.,
Kost J. T.,
Misty G. C.,
Wenning L. A.,
Breidinger S. A.,
Marbury T. C.,
Stone J. A.,
Gottesdiener K. M.,
Bloomfield D. M.,
Wagner J. A.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008318007
Subject(s) - raltegravir , medicine , moxifloxacin , qt interval , placebo , crossover study , pharmacology , pharmacodynamics , confidence interval , integrase inhibitor , anesthesia , pharmacokinetics , cardiology , human immunodeficiency virus (hiv) , chemistry , antiretroviral therapy , antibiotics , biochemistry , alternative medicine , family medicine , pathology , viral load
Raltegravir is a novel HIV‐1 integrase inhibitor with potent in vitro activity (IC 95 = 31 nM in 50% human serum). A double‐blind, randomized, placebo‐controlled, double‐dummy, 3‐period, single‐dose crossover study was conducted; subjects received single oral doses of 1600 mg raltegravir, 400 mg moxifloxacin, and placebo. The upper limit of the 2‐sided 90% confidence interval for the QTcF interval placebo‐adjusted mean change from baseline of raltegravir was less than 10 ms at every time point. For the raltegravir and placebo groups, there were no QTcF values >450 ms or change from baseline values >30 ms. A mean C max of ∼20 μM raltegravir was attained, ∼4‐fold higher than the C max at the clinical dose. Moxifloxacin demonstrated an increase in QTcF at the 2‐, 3‐, and 4‐hour time points. Administration of a single supratherapeutic dose of raltegravir does not prolong the QTcF interval. A single supratherapeutic dose design may be appropriate for crossover thorough QTc studies.