舍曲林在儿童和青少年住院治疗中心的药理学检测和治疗药物监测:一项试点研究。

Kate France, David Ammend, Jacob Brown
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引用次数: 1

摘要

背景:舍曲林常用于儿童焦虑和重度抑郁症的治疗,部分由CYP2C19代谢。虽然存在基于CYP2C19基因型的剂量建议,但儿童中关于舍曲林浓度与CYP2C19基因型之间关系的数据很少。此外,虽然在美国很少使用,但治疗药物监测也可以帮助指导剂量。本初步研究的主要目的是比较舍曲林浓度与CYP2C19基因型的关系。次要目标包括探索在儿童和青少年住院治疗中心使用药物遗传检测和治疗药物监测的可行性。方法:本研究是一项前瞻性、开放标签研究,研究对象是在儿童和青少年住院治疗中心接受舍曲林治疗的儿童。如果患者年龄小于18岁,服用舍曲林至少2周,使其达到稳定的浓度,通过住院治疗计划进行治疗,能够理解和说英语,则将其纳入研究范围。结果:共有20名参与者(80%为女性)完成了包括药理学检测和治疗药物监测在内的所有研究程序,平均年龄15.4岁(范围9-17岁)。40% (n=8)的参与者被诊断为广泛性焦虑症,而30% (n=6)的参与者被诊断为重度抑郁症。总体而言,舍曲林和去甲基舍曲林的平均浓度分别为21.1 ng/ml(范围:1-78 ng/ml)和52.4 ng/ml(范围:1-258 n/ml)。根据CYP2C19基因型,正常代谢者占60% (n=12),中间代谢者占10% (n=2),快速代谢者占30% (n=6)。每日舍曲林剂量(mg/天)在舍曲林(p2=0.62)和去甲基舍曲林浓度(p2=0.45)的观察变异性中占很大比例。在比较舍曲林和去甲基舍曲林的体重剂量时,舍曲林的体重日剂量(mg/kg/天)也占了舍曲林(p2=0.60)和去甲基舍曲林(p2=0.59)浓度差异的很大一部分。CYP2C19中间代谢、正常代谢和快速代谢的平均日剂量和基于体重的剂量分别为75 mg/天、87.5 mg/天、79.2 mg/天、1.5 mg/kg/天、1.3 mg/kg/天和1.1 mg/kg/天,尽管这些差异不显著。结论:这项小规模的初步研究显示舍曲林剂量与舍曲林和去甲基舍曲林浓度显著相关。CYP2C19代谢物组之间没有发现差异,可能是由于样本量有限。这些结果还表明,在儿童和青少年住院治疗中心设置药物遗传检测和治疗药物监测是可行的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Pharmacogenetic Testing and Therapeutic Drug Monitoring Of Sertraline at a Residential Treatment Center for Children and Adolescents: A Pilot Study.

Pharmacogenetic Testing and Therapeutic Drug Monitoring Of Sertraline at a Residential Treatment Center for Children and Adolescents: A Pilot Study.

Pharmacogenetic Testing and Therapeutic Drug Monitoring Of Sertraline at a Residential Treatment Center for Children and Adolescents: A Pilot Study.
Abstract Background: Sertraline is commonly prescribed to children for the treatment of anxiety and major depressive disorder and is metabolized in part by CYP2C19. While dosing recommendations based on CYP2C19 genotype exist, there is sparse data in children on the relationship between sertraline concentrations and CYP2C19 genotype. Additionally, although rarely utilized in the United States, therapeutic drug monitoring can also help to guide dosing. The primary objective of this pilot study was to compare sertraline concentrations with CYP2C19 genotype. Secondary objectives included exploring the feasibility of using pharmacogenetic testing and therapeutic drug monitoring in a residential treatment center for children and adolescents. Methods: This study was a prospective, open-label study of children prescribed sertraline being treated at a residential treatment center for children and adolescents. Individuals were included if they were < 18 years of age, taking sertraline for at least 2 weeks allowing them to reach steady-state concentrations, being treated through the residential treatment program, and able to understand and speak English. Results: A total of 20 participants (80% female) completed all study procedures, including pharmacogenetic testing and therapeutic drug monitoring, with an average age of 15.4 years (range: 9-17 years). Forty percent (n=8) of participants had a diagnosis of Generalized Anxiety Disorder, while 30% (n=6) had a diagnosis of Major Depressive Disorder. Overall, average sertraline and desmethylsertraline concentrations were 21.1 ng/ml (range: 1-78 ng/ml) and 52.4 ng/ml (range: 1-258 n/ml). Based on CYP2C19 genotypes, 60% (n=12) were normal metabolizers, 10% (n=2) were intermediate metabolizers, and 30% (n=6) were rapid metabolizers. Daily sertraline dose (mg/day) accounted for a significant amount of the observed variability in sertraline (p<0.0001; r2=0.62) and desmethylsertraline concentrations (p<0.001; r2=0.45). When comparing weight-based dosing by sertraline and desmethylsertraline concentrations, sertraline daily dose by weight (mg/kg/day) also accounted for a significant amount of the observed variability in sertraline (p<0.0001; r2=0.60) and desmethylsertraline (p<0.0001; r2=0.59) concentrations. Average daily and weight-based doses for CYP2C19 intermediate, normal, and rapid metabolizers were 75 mg/day, 87.5 mg/day, and 79.2 mg/day and 1.5 mg/kg/day, 1.3 mg/kg/day, and 1.1 mg/kg/day, though these were not significantly different. Conclusion: This small, pilot study showed sertraline dose to be significantly associated with sertraline and desmethylsertraline concentrations. No differences were noted between CYP2C19 metabolizer groups, likely due to the limited sample size. These results also suggest that ordering pharmacogenetic testing and therapeutic drug monitoring in the setting of a child and adolescent residential treatment center is feasible.
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