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Effects of Milnacipran on Cardiac Repolarization in Healthy Participants
Author(s) -
Periclou Antonia,
Palmer Robert H.,
Zheng Hongjie,
Lindamood Charles
Publication year - 2010
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 - 10.1177/0091270009346059
Subject(s) - milnacipran , qt interval , medicine , placebo , confidence interval , anesthesia , heart rate , prolongation , ventricular repolarization , cardiology , repolarization , antidepressant , electrophysiology , alternative medicine , pathology , hippocampus , blood pressure
Milnacipran is approved for management of fibromyalgia in the United States. In this double‐blind, placebo‐ and active drug‐controlled study (N = 100), effects of supratherapeutic doses of milnacipran on cardiac repolarization were evaluated in healthy volunteers. The primary outcome was the largest mean difference between milnacipran and placebo in time‐matched baseline‐adjusted QT interval corrected for heart rate using an individual correction formula (QTcNi). In addition, data were analyzed using the Fridericia formula (QTcF) and a post hoc piecewise QTcNi analysis based on a dichotomous cut of RR interval data at 800 ms. Moxifloxacin (400 mg single dose) was used to establish assay sensitivity. Using the QTcNi method, the largest difference in baseline‐adjusted QTcNi between milnacipran 300 mg bid and placebo was −4.7 ms (90% confidence interval [CI]: −9.4 to −0.1), indicating no QT prolongation. Analysis using the Fridericia formula (QTcF) showed a maximum adjusted mean change of +7.7 ms, but QTcF versus RR interval plots indicated overcorrection with this method. The piecewise QTcNi correction method demonstrated a more accurate correction for drug‐induced heart rate increase; mean baseline‐adjusted between‐group difference was +0.9 ms (90% CI: −6.6 to 8.3). The results suggest that milnacipran would not significantly affect cardiac repolarization at clinically relevant therapeutic and supratherapeutic concentrations.