Fonseca Francina, Marti-Almor Julio, Pastor Antoni, Cladellas Mercè, Farré Magí, de la Torre Rafael, Torrens Marta
Drug Addiction Unit, IAPS-Hospital del Mar, Passeig Marítim 25-29, 08003 Barcelona, Spain.
Drug Alcohol Depend. 2009 Jan 1;99(1-3):327-32. doi: 10.1016/j.drugalcdep.2008.06.018. Epub 2008 Sep 5.
There is a concern about cardiac rhythm disorders related to QTc interval prolongation induced by methadone. A cross-sectional study was designed to evaluate the prevalence of long QTc (LQTc) interval in patients in methadone maintenance treatment (MMT) and risk factors for LQTc.
The study population included 109 subjects (74 males, median age 43 years). Socio-demographic and toxicological variables were recorded, as well as concomitant use of drugs related with QT prolongation, history of heart diseases, and corrected QT interval by heart rate (QTc) in the ECG. Plasma concentrations of (R)-methadone and (S)-methadone enantiomers were determined in 69 subjects.
Ten patients (9.2%) presented a QTc above 440 ms but a QTc above 500 ms was observed in only 2 (1.8%). Patients with QTc above 440 ms compared with the remaining subjects were older (median [25th-75th percentile range]: 49 [39-56] years vs. 37 [33-43]; Wilcoxon's W=217.5, p=0.002) and took a higher daily dose of methadone (median [25th-75th percentile range]: 120 [66-228] mg/day vs. 60 [40-110] mg/day; W=298.5, p=0.037). Methadone dose correlated with QTc interval (Pearson's r(2)=0.291, p=0.002). Patients with and without long QTc showed no differences in plasma concentrations of (R)-methadone and (S)-methadone enantiomers.
The prevalence of LQTc was 9.2%. An association between LQTc and methadone doses was observed but the relationship with plasma concentrations of methadone enantiomers is unclear.
美沙酮引起的QTc间期延长所导致的心律失常令人担忧。一项横断面研究旨在评估接受美沙酮维持治疗（MMT）的患者中长QTc（LQTc）间期的患病率以及LQTc的危险因素。
研究人群包括109名受试者（74名男性，中位年龄43岁）。记录社会人口统计学和毒理学变量，以及与QT延长相关的药物的合并使用情况、心脏病史和心电图中根据心率校正的QT间期（QTc）。在69名受试者中测定了（R）-美沙酮和（S）-美沙酮对映体的血浆浓度。
10名患者（9.2%）的QTc超过440毫秒，但只有2名患者（1.8%）的QTc超过500毫秒。QTc超过440毫秒的患者与其余受试者相比年龄更大（中位值[第25-75百分位数范围]：49[39-56]岁对37[33-43]岁；Wilcoxon秩和检验W=217.5，p=0.002），且每日美沙酮剂量更高（中位值[第25-75百分位数范围]：120[66-228]毫克/天对[40-110]毫克/天；W=298.5，p=0.037）。美沙酮剂量与QTc间期相关（Pearson相关系数r²=0.291，p=0.002）。有和没有长QTc的患者在（R）-美沙酮和（S）-美沙酮对映体的血浆浓度上没有差异。
LQTc的患病率为9.2%。观察到LQTc与美沙酮剂量之间存在关联，但与美沙酮对映体血浆浓度的关系尚不清楚。
