Ključević Željko, Benzon Benjamin, Ključević Nikola, Veršić Bratinčević Maja, Sutlović Davorka
Željko Ključević, Public Health Institute of Split-Dalmatia County, Vukovarska 46, 21 000 Split, Croatia,
Croat Med J. 2018 Dec 31;59(6):298-306. doi: 10.3325/cmj.2018.59.298.
To assess the effect of liver damage on methadone metabolism in opiate addicts undergoing methadone maintenance treatment (MMT).
This cross-sectional study recruited 74 patients treated at the outpatient clinic of Public Health Institute of Split-Dalmatia County from 2013-2016. Concentrations of methadone and its main inactive metabolite were measured in participants' biological samples on regular check-ups. Urine samples obtained before oral methadone intake, and blood and urine samples obtained 90 minutes after methadone intake were analyzed using gas chromatography/mass spectrometry. Participants were divided into groups according to liver damage criteria: hepatitis C virus status (positive, negative, or clinical remission); aspartate aminotransferase to platelet ratio (APRI) index (<0.7 and ≥0.7); and fibrosis-4 score (<1.45, 1.45-3.25, >3.25).
Metabolic ratio and methadone metabolite concentration in plasma decreased linearly with HCV infection status by the factor of 1.67 (P=0.001) and 2.2 (P=0.043), respectively. Metabolic ratio in plasma decreased in patients with APRI index ≥0.7 by the average factor of 2.12 (P=0.01) and methadone metabolite concentration in plasma decreased by the factor of 6.16 (P=0.009). Metabolic ratio in urine decreased with the severity of fibrosis-4 score by the average factor of 1.63 (P=0.008), whereas methadone metabolite concentration decreased by the factor of 3.53 (P=0.007).
Liver damage decreases methadone metabolism. Indices of liver function should be calculated regularly during MMT for methadone dose titration.
评估肝脏损害对接受美沙酮维持治疗(MMT)的阿片类成瘾者美沙酮代谢的影响。
这项横断面研究招募了2013年至2016年在斯普利特 - 达尔马提亚县公共卫生研究所门诊接受治疗的74例患者。在定期检查时测量参与者生物样本中美沙酮及其主要无活性代谢物的浓度。使用气相色谱/质谱法分析口服美沙酮前采集的尿液样本,以及美沙酮摄入90分钟后采集的血液和尿液样本。根据肝脏损害标准将参与者分为几组:丙型肝炎病毒状态(阳性、阴性或临床缓解);天冬氨酸转氨酶与血小板比值(APRI)指数(<0.7和≥0.7);以及纤维化 - 4评分(<1.45、1.45 - 3.25、>3.25)。
血浆中的代谢率和美沙酮代谢物浓度随丙型肝炎病毒感染状态分别以1.67倍(P = 0.001)和2.2倍(P = 0.043)的幅度呈线性下降。APRI指数≥0.7的患者血浆中的代谢率平均下降2.12倍(P = 0.01),血浆中美沙酮代谢物浓度下降6.16倍(P = 0.009)。尿液中的代谢率随纤维化 - 4评分的严重程度平均下降1.63倍(P = 0.008),而美沙酮代谢物浓度下降3.53倍(P = 0.007)。
肝脏损害会降低美沙酮代谢。在MMT期间应定期计算肝功能指标以进行美沙酮剂量滴定。