Differences in Duloxetine Dosing Strategies in Smoking and Nonsmoking Patients: Therapeutic Drug Monitoring Uncovers the Impact on Drug Metabolism
Differences in Duloxetine Dosing Strategies in Smoking and Nonsmoking Patients: Therapeutic Drug Monitoring Uncovers the Impact on Drug Metabolism
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DOI：
10.4088/jcp.17m12086
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发表时间：
2018-09-01
影响因子：
5.3
通讯作者：
Paulzen, Michael
中科院分区：
文献类型：
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作者：
Augustin, Marc;Schoretsanitis, Georgios;Paulzen, Michael
背景：对于某些精神药物，如氯氮平或奥氮平，吸烟对药物代谢的影响已得到充分研究。烟草烟雾增加了药物的代谢，这些药物是细胞色素P450（CYP 1A 2）1A 2的底物，这是由于CYP 1A 2的诱导。抗抑郁药度洛沙汀作为一种去甲肾上腺素再摄取抑制剂，主要通过CYP 1A 2代谢。到目前为止，很少有人知道吸烟对血清度洛沙汀concentration.Methods的影响：治疗药物监测数据库组成的血浆浓度的度洛沙汀收集2013年1月至2017年6月进行了分析。一组接受度洛塞汀治疗的非吸烟患者（n = 89）与一组也接受度洛塞汀治疗的活跃吸烟者（n = 36）进行了比较。使用非参数tests.Results比较了度洛沙坦的血清浓度和剂量调整后的血清浓度：各组在性别方面没有差异（P = 0.063），但主动吸烟者组更年轻（P <0.001），接受的度洛沙坦日剂量更高（P = 0.001）。吸烟者的中位血清度洛沙汀浓度显著降低（降低38.4%，P = 0.002），剂量调整后的血清浓度降低53.6%（吸烟者为0.325 [ng/mL]/[mg/d]，非吸烟者为0.7 [ng/mL]/[mg/d]，P <0.001）。烟草烟雾对CYP 1A 2的诱导是作为CYP 1A 2底物的药物的临床相关因素。临床医生应积极评估吸烟状况，告知患者吸烟对度洛沙汀代谢的影响，并预期戒烟后血清浓度会升高。治疗药物监测通过实现治疗的个性化来确保治疗疗效，因为吸烟者需要更高的度洛沙汀剂量以将血清浓度目标在治疗参考范围内。
Background: For certain psychotropic drugs, such as clozapine or olanzapine, the influence of smoking on drug metabolism is well studied. Tobacco smoke increases the metabolism of drugs that are substrates for cytochrome P450 (CYP) 1A2 due to CYP induction. The antidepressant duloxetine, acting as a serotonin-norepinephrine reuptake inhibitor, is mainly metabolized via CYP1A2. To date, little is known about the influence of smoking on serum duloxetine concentrations.Methods: A therapeutic drug monitoring database consisting of plasma concentrations of duloxetine collected from January 2013 to June 2017 was analyzed. A group of nonsmoking patients undergoing treatment with duloxetine (n = 89) was compared to a group of active smokers also receiving duloxetine (n = 36). Serum concentrations of duloxetine and dose-adjusted serum concentrations were compared using non-parametric tests.Results: Groups did not differ concerning sex (P = .063), but the group of active smokers was younger (P < .001) and received higher daily doses of duloxetine (P = .001). Smokers showed significantly lower median serum duloxetine concentrations (38.4% lower, P = .002) and 53.6% lower dose-adjusted serum concentrations (0.325 [ng/mL]/[mg/d] in smokers vs 0.7 [ng/mL]/[mg/d] in nonsmokers, P < .001).Conclusions: Despite higher daily doses, smokers had considerably lower serum duloxetine concentrations. The induction of CYP1A2 by tobacco smoke is a clinically relevant factor for drugs that are substrates for CYP1A2. Clinicians should actively assess smoking status, inform patients about the effect of smoking on duloxetine metabolism, and anticipate higher serum concentrations in the case of smoking cessation. Therapeutic drug monitoring ensures treatment efficacy by enabling the personalizing of treatment, as smokers need higher duloxetine doses to target serum concentrations within the therapeutic reference range.