Lamotrigine does not prolong QTc in a thorough QT/QTc study in healthy subjects.
Br J Clin Pharmacol
; 66(3): 396-404, 2008 Sep.
Article
em En
| MEDLINE
| ID: mdl-18662287
ABSTRACT
AIM:
To characterize the effects of lamotrigine on QT interval in healthy subjects.METHODS:
Healthy subjects received a single oral dose of moxifloxacin (400 mg) or placebo in crossover design, followed by a dose-escalating regimen of lamotrigine (n = 76) over a 77-day period, or matched placebo (n = 76). Blood samples were taken for determination of moxifloxacin and lamotrigine concentrations and digital 12-lead ECGs were recorded. The relationships between individual QT values and respective individual moxifloxacin or lamotrigine concentrations were explored using population pharmacokinetic-pharmacodynamic (PK-PD) modelling.RESULTS:
Moxifloxacin was associated with a maximum mean increase from baseline in QTcF of 14.81 ms [90% confidence interval (CI) 13.50, 16.11] 2.5 h after dosing. Steady-state exposure to lamotrigine (50, 150 or 200 mg b.d.) was not associated with an increase in QTc interval. Small reductions in QTcF (maximum mean difference from placebo -7.48 ms, 90% CI -10.49, -4.46) and small increases in heart rate (maximum mean difference from placebo 5.94 bpm, 90% CI 3.81, 8.06) were observed with lamotrigine 200 mg b.d. vs. placebo. No effect of lamotrigine on QRS duration or blood pressure was observed. No outliers with QTcF > 450 ms, or with an increase from baseline of >60 ms were observed in the lamotrigine group. PK-PD modelling indicated statistically significant decreases in individually corrected QT intervals for lamotrigine and statistically significant increases in individually corrected QT intervals for moxifloxacin over the concentration ranges studied.CONCLUSIONS:
Therapeutic doses of lamotrigine (50-200 mg b.d.) were not associated with QT prolongation in healthy subjects.
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Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Compostos Aza
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Triazinas
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Síndrome do QT Longo
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Eletrocardiografia
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Antiarrítmicos
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article