唾液和血清中安非他命浓度与儿童和青少年注意缺陷多动障碍的关系。

Relationship Between Amphetamine Concentrations in Saliva and Serum in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder.

机构信息

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg; and.

Institute for Pharmacy and Food Chemistry, University of Würzburg, Würzburg, Germany.

出版信息

Ther Drug Monit. 2021 Aug 1;43(4):564-569. doi: 10.1097/FTD.0000000000000831.

DOI:10.1097/FTD.0000000000000831

PMID:33149054

Abstract

BACKGROUND

Therapeutic drug monitoring (TDM) is a valid tool for the optimization of psychopharmacotherapy; however, in child and adolescent psychiatry, uncomfortable intravenous sample collection is the main challenge and restricts the use of TDM. Therefore, it is important to evaluate alternate specimens to facilitate TDM. The aim of this study was to evaluate the feasibility of using saliva for the TDM of amphetamine in children and adolescents with attention-deficit/hyperactivity disorder.

METHODS

In this study, 28 patient samples (mean age, 11.3 years; boys, 23; and girls, 5) treated with lisdexamfetamine were included. The active compound amphetamine was extracted and derivatized before quantification by high-performance liquid chromatography with fluorescence detection. Nonparametric Spearman rank correlations were used for correlation analyses; for clinical validation, Bland-Altman analysis was applied.

RESULTS

The median amphetamine concentrations in saliva were 2.7 times higher (range 0.7-23.6) than those in serum (257.8 ng/mL versus 77.2 ng/mL; z = -4.51, P < 0.001). A strong positive linear correlation was observed between saliva and serum concentrations (ρ = 0.628, P < 0.001). The ratio of saliva-to-serum concentration was strongly pH dependent (ρ = -0.712, P < 0.001). Therefore, a transformation formula, factoring in salivary pH, to calculate serum concentrations from the measured saliva concentrations was applied. Theoretical and measured serum amphetamine concentrations were subjected to Bland-Altman analysis. Using an acceptance limit of 20%, only 21% (n = 6) of samples fulfilled this criterion.

CONCLUSIONS

Amphetamine paired saliva-to-serum concentrations were highly variable and strongly affected by salivary pH, indicating that saliva is an inappropriate sampling matrix for TDM of amphetamine. Furthermore, Bland-Altman analysis did not support saliva as a suitable matrix for TDM.

摘要

背景

治疗药物监测（TDM）是优化精神药理学治疗的有效工具；然而，在儿童和青少年精神病学中，令人不适的静脉样本采集是主要挑战，限制了 TDM 的使用。因此，评估替代样本以促进 TDM 非常重要。本研究旨在评估使用唾液作为儿童和青少年注意力缺陷/多动障碍患者中安非他命 TDM 的可行性。

方法

在这项研究中，纳入了 28 名接受 lisdexamfetamine 治疗的患者样本（平均年龄 11.3 岁；男孩 23 名，女孩 5 名）。通过高效液相色谱法荧光检测提取和衍生安非他命后进行定量。使用非参数 Spearman 秩相关进行相关性分析；为了临床验证，应用了 Bland-Altman 分析。

结果

唾液中的安非他命浓度中位数（范围 0.7-23.6）是血清浓度（257.8ng/mL 与 77.2ng/mL；z=-4.51，P<0.001）的 2.7 倍。观察到唾液和血清浓度之间存在强烈的正线性相关性（ρ=0.628，P<0.001）。唾液与血清浓度的比值强烈依赖于 pH（ρ=-0.712，P<0.001）。因此，应用了一个转化公式，考虑了唾液 pH，用于根据测量的唾液浓度计算血清浓度。对理论和测量的血清安非他命浓度进行了 Bland-Altman 分析。使用 20%的接受限值，只有 21%（n=6）的样本符合该标准。