Dried Blood Spot (DBS) as a useful tool to improve clozapine, aripiprazole and paliperidone treatment: From adherence to efficiency

IF 5.2 3区医学 Q1 PSYCHIATRY

Revista de psiquiatria y salud mental Pub Date : 2022-10-01 DOI:10.1016/j.rpsm.2022.04.002

Miguel Bernardo , Gisela Mezquida , Paula Ferré , Bibiana Cabrera , Mercè Torra , Ana Maria Lizana , Mercè Brunet

{"title":"Dried Blood Spot (DBS) as a useful tool to improve clozapine, aripiprazole and paliperidone treatment: From adherence to efficiency","authors":"Miguel Bernardo , Gisela Mezquida , Paula Ferré , Bibiana Cabrera , Mercè Torra , Ana Maria Lizana , Mercè Brunet","doi":"10.1016/j.rpsm.2022.04.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Therapeutic Drug Monitoring<span> (TDM) of antipsychotics in schizophrenia is a powerful tool that allows tailoring the treatment in an individualized approach. Our goals are to develop and validate a Dried Blood Spot (DBS) method for monitoring some commonly used antipsychotics (aripiprazole, clozapine, and paliperidone) and to evaluate its usefulness as a compliance biomarker, as well as in drug-dose adjustment to personalize the antipsychotic treatment to improve its efficacy and safety.</span></p></div><div><h3>Methods</h3><p>31 first-psychotic episode (FEP) and schizophrenia patients were included; 5 refer to naïve FEP who started antipsychotic treatment; 26, to patients with more than one episode and under antipsychotic treatment: aripiprazole (7 cases), clozapine (17), paliperidone (11). For DBS sample collection, 25μl of capillary blood were placed in the spot of a FTA™DMPK-C-card. After completely dryness, antipsychotics were extracted and analyzed by a validated UHPLC-MS/MS-method. DBS antipsychotic results were compared with those obtained in venous blood/plasma.</p></div><div><h3>Results</h3><p>Aripiprazole, paliperidone and clozapine showed from good to excellent correlations between concentrations in venous blood and DBS capillary blood (<em>r</em><sup>2</sup>, from 0.500 to 0.721). The correlation between conventional plasma and DBS concentrations for paliperidone, aripiprazole, clozapine, and their metabolites were moderate, suggesting that optimal drug target concentrations should be established for DBS.</p></div><div><h3>Conclusions</h3><p>In this study, for aripiprazole, dehydroaripiprazole, paliperidone, clozapine and desmethylclozapine, DBS has provided good analytical performance for TDM. Thus, DBS sampling can offer a great alternative over conventional sampling for plasma measurement. The assay provides good analytical performances for TDM and clinical research applicability, suggesting that DBS is a promising clinical application in TDM in psychiatry.</p></div>","PeriodicalId":21391,"journal":{"name":"Revista de psiquiatria y salud mental","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Revista de psiquiatria y salud mental","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1888989122000349","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}

引用次数: 4

Abstract

Introduction

Therapeutic Drug Monitoring (TDM) of antipsychotics in schizophrenia is a powerful tool that allows tailoring the treatment in an individualized approach. Our goals are to develop and validate a Dried Blood Spot (DBS) method for monitoring some commonly used antipsychotics (aripiprazole, clozapine, and paliperidone) and to evaluate its usefulness as a compliance biomarker, as well as in drug-dose adjustment to personalize the antipsychotic treatment to improve its efficacy and safety.

Methods

31 first-psychotic episode (FEP) and schizophrenia patients were included; 5 refer to naïve FEP who started antipsychotic treatment; 26, to patients with more than one episode and under antipsychotic treatment: aripiprazole (7 cases), clozapine (17), paliperidone (11). For DBS sample collection, 25 μl of capillary blood were placed in the spot of a FTA™DMPK-C-card. After completely dryness, antipsychotics were extracted and analyzed by a validated UHPLC-MS/MS-method. DBS antipsychotic results were compared with those obtained in venous blood/plasma.

Results

Aripiprazole, paliperidone and clozapine showed from good to excellent correlations between concentrations in venous blood and DBS capillary blood (r², from 0.500 to 0.721). The correlation between conventional plasma and DBS concentrations for paliperidone, aripiprazole, clozapine, and their metabolites were moderate, suggesting that optimal drug target concentrations should be established for DBS.

Conclusions

In this study, for aripiprazole, dehydroaripiprazole, paliperidone, clozapine and desmethylclozapine, DBS has provided good analytical performance for TDM. Thus, DBS sampling can offer a great alternative over conventional sampling for plasma measurement. The assay provides good analytical performances for TDM and clinical research applicability, suggesting that DBS is a promising clinical application in TDM in psychiatry.

查看原文本刊更多论文

干血斑(DBS)作为改善氯氮平、阿立哌唑和帕利哌酮治疗的有用工具:从依从性到有效性

精神分裂症患者抗精神病药物的治疗性药物监测(TDM)是一种强有力的工具，它允许以个性化的方法定制治疗。我们的目标是开发和验证一种干血斑(DBS)方法，用于监测一些常用的抗精神病药物(阿立哌唑、氯氮平和帕利哌酮)，并评估其作为依从性生物标志物的有效性，以及在药物剂量调整方面的有效性，以个性化抗精神病药物治疗，提高其有效性和安全性。方法纳入31例首发精神病发作(FEP)和精神分裂症患者;5 .参考naïve FEP者开始抗精神病药物治疗;26例，一次以上发作并接受抗精神病药物治疗的患者:阿立哌唑(7例)，氯氮平(17例)，帕利哌酮(11例)。DBS采集时，取25 μl毛细血管血置于FTA™dmpk -c卡上。完全干燥后，提取抗精神病药物，采用高效液相色谱-质谱联用法进行分析。DBS抗精神病结果与静脉血/血浆比较。结果阿立哌唑、帕利哌酮和氯氮平静脉血浓度与DBS毛细血管血浓度呈从良好到极好的相关性(r2为0.500 ~ 0.721)。帕利哌酮、阿立哌唑、氯氮平及其代谢物的常规血浆浓度与DBS浓度的相关性为中等，提示DBS的最佳药物靶浓度应确定。结论在本研究中，对于阿立哌唑、脱氢阿立哌唑、帕利哌酮、氯氮平和去甲基氯氮平，DBS对TDM具有良好的分析性能。因此，DBS采样可以为等离子体测量提供比传统采样更好的选择。该方法对TDM具有良好的分析性能和临床研究适用性，提示DBS在精神病学TDM的临床应用前景广阔。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Revista de psiquiatria y salud mental PSYCHIATRY-

自引率

3.30%

发文量

期刊介绍： The Spanish Journal of Psychiatry and Mental Health (SJPMH), incorporated into ISSN 1888-9891, is the official scientific publication of the Spanish Society of Psychiatry and Mental Health. The journal focuses on studying mental illnesses, their pathological processes, and their psychosocial consequences, and aims to disseminate scientific advances in all areas related to mental health and illness. SJPMH accepts unpublished works on psychiatry and mental health, including their medical and social implications. The journal provides space for research in the biological, clinical, and psychosocial fields. Manuscripts undergo peer-review by external reviewers before being accepted for publication. SJPMH is indexed in Index Medicus/Medline, IBECS, Social Sciences Citation Index Journal Citation Reports/Social Sciences Edition, and Current Contents/Social and Behavioral Sciences.