用于优化安非他酮治疗的抑郁症患者剂量的羟安非他酮血清浓度。

Serum concentrations of hydroxybupropion for dose optimization of depressed patients treated with bupropion.

作者信息

Laib Anne K, Brünen Sonja, Pfeifer Philippe, Vincent Philippe, Hiemke Christoph

机构信息

*Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Mainz, Germany; †Department of Pharmacy, Institut universitaire en santé mentale de Montréal, Faculty of Pharmacy, Université de Montréal, Montreal, Canada; and ‡Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Mainz, Germany.

出版信息

Ther Drug Monit. 2014 Aug;36(4):473-9. doi: 10.1097/FTD.0000000000000042.

DOI:10.1097/FTD.0000000000000042

PMID:24452068

Abstract

BACKGROUND

Bupropion is a dopamine and norepinephrine reuptake inhibitor approved for the treatment of depression and smoking cessation. According to the recently published reviews, it is a candidate for therapeutic drug monitoring (TDM) to improve therapeutic outcomes and reduce risks of intolerability or intoxication. In practice, however, the use of TDM is limited due to the chemical instability of bupropion. This investigation sought to determine if the major, active, and chemically stable metabolite 4-hydroxybupropion is a suitable measure to guide antidepressant drug therapy with bupropion.

METHODS

4-Hydroxybupropion serum levels were measured using a newly developed and validated high-performance liquid chromatography assay with ultraviolet detection. They correlated with therapeutic effects measured by the clinical global impression scale for improvement.

RESULTS

The study included 52 patients (50% women). Patients who were markedly improved according to the clinical global impression scale score had significantly (P = 0.042) higher 4-hydroxybupropion serum levels than those with moderate or minimal improvement (mean ± SD, 1113 ± 576, 825 ± 398, and 475 ± 331 ng/mL, respectively). Analysis of receiver operating characteristics revealed significant predictive properties of 4-hydroxybupropion serum levels (P = 0.002) for marked improvement with a lower threshold level of 858 ng/mL. Under similar mean doses (265 ± 107 versus 239 ± 100 mg, respectively), women attained significantly higher serum levels than men (1050 ± 524 versus 589 ± 352 ng/mL, respectively) and exhibited a better therapeutic effect (P = 0.018).

CONCLUSIONS

Despite multiple limitations of this naturalistic study, evidence could be given that the measurement of 4-hydroxybupropion in serum is suitable to perform TDM for bupropion. Blood levels should be above 860 ng/mL to attain therapeutic improvement. Potential sex differences in bupropion pharmacokinetics, probably due to differential activities of CYP2B6, should be taken into account when the drug is prescribed.

摘要

背景

安非他酮是一种多巴胺和去甲肾上腺素再摄取抑制剂，已被批准用于治疗抑郁症和戒烟。根据最近发表的综述，它是治疗药物监测（TDM）的候选药物，以改善治疗效果并降低不耐受或中毒风险。然而，在实践中，由于安非他酮的化学不稳定，TDM的应用受到限制。本研究旨在确定主要的、活性的和化学稳定的代谢物4-羟基安非他酮是否是指导安非他酮抗抑郁药物治疗的合适指标。

方法

采用新开发并验证的高效液相色谱紫外检测法测定4-羟基安非他酮血清水平。它们与临床总体印象改善量表测量的治疗效果相关。

结果

该研究纳入了52例患者（50%为女性）。根据临床总体印象量表评分显著改善的患者，其4-羟基安非他酮血清水平显著高于改善程度为中度或轻度的患者（P = 0.042）（均值±标准差分别为1113±576、825±398和475±331 ng/mL）。受试者工作特征分析显示，4-羟基安非他酮血清水平具有显著的预测特性（P = 0.002），对于显著改善，较低阈值水平为858 ng/mL。在相似的平均剂量下（分别为265±107和239±100 mg），女性的血清水平显著高于男性（分别为1050±524和589±352 ng/mL），并且表现出更好的治疗效果（P = 0.018）。