Mijatović Vesna, Samojlik Isidora, Petković Stojan, Vukmirović Saša, Uvelin Arsen, Dickov Aleksandra
a Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine , University of Novi Sad , Novi Sad , Serbia.
b Department of Forensic Medicine, Faculty of Medicine , University of Novi Sad , Novi Sad , Serbia.
Expert Opin Drug Saf. 2017 Dec;16(12):1323-1328. doi: 10.1080/14740338.2017.1382470. Epub 2017 Sep 26.
The aim is to evaluate the role of diazepam concentrations in development of low-concentration-methadone-associated QTc prolongation in patients with opioid use disorder during methadone maintenance treatment (MMT) induction.
Individuals with addiction disorder on MMT were studied before the beginning of MMT and after one and six months of MMT. Serum concentrations of methadone, diazepam, electrolytes and ECG were analyzed.
Thirty patients were enrolled. The mean methadone concentration at time points was 177 ± 119 ng/ml and 343 ± 182 ng/ml, while the mean diazepam concentration was 561 ± 437 ng/ml and 1045 ± 933 ng/ml. The QTc interval before the introduction of MMT, after 1 and 6 months of MMT were 412 ± 27 ms, 425 ± 18 ms and 424 ± 15 ms, respectively, showing statistically significant increase in the length of QTc interval after 1 and 6 months of MMT. Statistically significant correlation between the concentration of methadone and QTc interval length at observed time points (R = 0.239, p = 0.018; R = 0.513, p = 0.006) was shown, and it remained so if the concentration of diazepam was included (R = 0.347, p = 0.026, R = 0.513, p = 0.009).
The prolongation of QTc below the risk threshold in low methadone therapeutic doses has been recorded and concomitant use of diazepam could be a co-factor in such issue.
目的是评估地西泮浓度在阿片类物质使用障碍患者美沙酮维持治疗（MMT）诱导期间低浓度美沙酮相关QTc延长发展中的作用。
对接受MMT的成瘾障碍患者在MMT开始前、MMT 1个月和6个月后进行研究。分析美沙酮、地西泮、电解质血清浓度和心电图。
纳入30例患者。各时间点美沙酮平均浓度分别为177±119 ng/ml和343±182 ng/ml，而地西泮平均浓度分别为561±437 ng/ml和1045±933 ng/ml。MMT开始前、MMT 1个月和6个月后的QTc间期分别为412±27 ms、425±18 ms和424±15 ms，显示MMT 1个月和6个月后QTc间期长度有统计学意义的增加。观察时间点美沙酮浓度与QTc间期长度之间存在统计学意义的相关性（R = 0.239，p = 0.018；R = 0.513，p = 0.006），如果纳入地西泮浓度，相关性依然存在（R = 0.347，p = 0.026，R = 0.513，p = 0.009）。
已记录到低美沙酮治疗剂量下QTc延长至风险阈值以下，同时使用地西泮可能是该问题的一个协同因素。
