The lowest effective plasma concentration of atomoxetine in pediatric patients with attention deficit/hyperactivity disorder: A non-randomized prospective interventional study
Atomoxetine (ATX) is used as a first-line, non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD), although no studies have systematically examined the relationship between plasma concentration and clinical efficacy. We conducted this non-randomized prospective interventional st...
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| Veröffentlicht in: | Medicine (Baltimore) 2021-07, Vol.100 (27), p.e26552-e26552 |
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| creator | Sugimoto, Atsunori Suzuki, Yutaro Orime, Naoki Hayashi, Taketsugu Yoshinaga, Kiyohiro Egawa, Jun Ono, Shin Sugai, Takuro Inoue, Yoshimasa Someya, Toshiyuki |
| description | Atomoxetine (ATX) is used as a first-line, non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD), although no studies have systematically examined the relationship between plasma concentration and clinical efficacy. We conducted this non-randomized prospective interventional study to examine the relationship between plasma concentration of ATX and clinical efficacy.
Forty-three ADHD pediatric patients received ATX, and the steady-state through plasma concentration of the last daily dose that was maintained for at least 4 weeks were determined by high-performance liquid chromatography.
The receiver operating characteristic curve suggested that when plasma concentration exceeded 64.60 ng/mL, scores on the ADHD-Rating Scale improved by 50% or more (P = .14). Although 6 of the 8 final responders were unresponsive at the initial dose (.72 ± .04 mg/kg [mean ± standard deviation]), they responded after increasing the ATX dose to the final dose (1.52 ± .31 mg/kg). Excluding 7 outlier participants, the concentration was 83.3 ± 32.3 ng/mL in 7 responders and was significantly higher than 29.5 ± 23.9 ng/mL (P |
| doi_str_mv | 10.1097/MD.0000000000026552 |
| format | Article |
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Forty-three ADHD pediatric patients received ATX, and the steady-state through plasma concentration of the last daily dose that was maintained for at least 4 weeks were determined by high-performance liquid chromatography.
The receiver operating characteristic curve suggested that when plasma concentration exceeded 64.60 ng/mL, scores on the ADHD-Rating Scale improved by 50% or more (P = .14). Although 6 of the 8 final responders were unresponsive at the initial dose (.72 ± .04 mg/kg [mean ± standard deviation]), they responded after increasing the ATX dose to the final dose (1.52 ± .31 mg/kg). Excluding 7 outlier participants, the concentration was 83.3 ± 32.3 ng/mL in 7 responders and was significantly higher than 29.5 ± 23.9 ng/mL (P < .01) for the 29 non-responders.
These results suggest that a minimum effective plasma concentration of ATX is required to achieve sufficient clinical efficacy. We hypothesized a mechanism that results in the realization of a clinical effect when the plasma concentration exceeds a certain threshold in the potential response group, whereas will not improve even if the plasma concentration is increased in the unqualified non-responder group.</description><identifier>ISSN: 0025-7974</identifier><identifier>EISSN: 1536-5964</identifier><identifier>DOI: 10.1097/MD.0000000000026552</identifier><identifier>PMID: 34232195</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins</publisher><subject>Adrenergic Uptake Inhibitors - pharmacokinetics ; Atomoxetine Hydrochloride - pharmacokinetics ; Attention Deficit Disorder with Hyperactivity - blood ; Attention Deficit Disorder with Hyperactivity - drug therapy ; Child ; Clinical Trial/Experimental Study ; Double-Blind Method ; Female ; Humans ; Male ; Prospective Studies ; Treatment Outcome</subject><ispartof>Medicine (Baltimore), 2021-07, Vol.100 (27), p.e26552-e26552</ispartof><rights>Lippincott Williams & Wilkins</rights><rights>Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.</rights><rights>Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3553-40265c2e1f2cff92536524eb29249b89a8dc6e3e1345288553aec9a5849336253</cites><orcidid>0000-0002-6684-0016</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270591/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270591/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34232195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sugimoto, Atsunori</creatorcontrib><creatorcontrib>Suzuki, Yutaro</creatorcontrib><creatorcontrib>Orime, Naoki</creatorcontrib><creatorcontrib>Hayashi, Taketsugu</creatorcontrib><creatorcontrib>Yoshinaga, Kiyohiro</creatorcontrib><creatorcontrib>Egawa, Jun</creatorcontrib><creatorcontrib>Ono, Shin</creatorcontrib><creatorcontrib>Sugai, Takuro</creatorcontrib><creatorcontrib>Inoue, Yoshimasa</creatorcontrib><creatorcontrib>Someya, Toshiyuki</creatorcontrib><title>The lowest effective plasma concentration of atomoxetine in pediatric patients with attention deficit/hyperactivity disorder: A non-randomized prospective interventional study</title><title>Medicine (Baltimore)</title><addtitle>Medicine (Baltimore)</addtitle><description>Atomoxetine (ATX) is used as a first-line, non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD), although no studies have systematically examined the relationship between plasma concentration and clinical efficacy. We conducted this non-randomized prospective interventional study to examine the relationship between plasma concentration of ATX and clinical efficacy.
Forty-three ADHD pediatric patients received ATX, and the steady-state through plasma concentration of the last daily dose that was maintained for at least 4 weeks were determined by high-performance liquid chromatography.
The receiver operating characteristic curve suggested that when plasma concentration exceeded 64.60 ng/mL, scores on the ADHD-Rating Scale improved by 50% or more (P = .14). Although 6 of the 8 final responders were unresponsive at the initial dose (.72 ± .04 mg/kg [mean ± standard deviation]), they responded after increasing the ATX dose to the final dose (1.52 ± .31 mg/kg). Excluding 7 outlier participants, the concentration was 83.3 ± 32.3 ng/mL in 7 responders and was significantly higher than 29.5 ± 23.9 ng/mL (P < .01) for the 29 non-responders.
These results suggest that a minimum effective plasma concentration of ATX is required to achieve sufficient clinical efficacy. We hypothesized a mechanism that results in the realization of a clinical effect when the plasma concentration exceeds a certain threshold in the potential response group, whereas will not improve even if the plasma concentration is increased in the unqualified non-responder group.</description><subject>Adrenergic Uptake Inhibitors - pharmacokinetics</subject><subject>Atomoxetine Hydrochloride - pharmacokinetics</subject><subject>Attention Deficit Disorder with Hyperactivity - blood</subject><subject>Attention Deficit Disorder with Hyperactivity - drug therapy</subject><subject>Child</subject><subject>Clinical Trial/Experimental Study</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Prospective Studies</subject><subject>Treatment Outcome</subject><issn>0025-7974</issn><issn>1536-5964</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctu1DAUhi0EokPhCZCQl2zSOr4kMQukquUmtWJT1pbHOSGGxA62M9PhpXhFHDKUizeWj7__9_F_EHpekrOSyPr85uqM_Fm0EoI-QJtSsKoQsuIP0SZXRVHLmp-gJzF-IaRkNeWP0QnjlNFSig36cdsDHvweYsLQdWCS3QGeBh1HjY13BlwKOlnvsO-wTn70d5CsA2wdnqC1OgVr8JSRTEa8t6nPWMqHRdNCZ41N5_1hgqAXc5sOuLXRhxbCK3yBnXdF0K71o_0OLZ6Cj9OxC-sShN3qpAcc09wenqJHnR4iPDvup-jT2ze3l--L64_vPlxeXBeGCcEKvuRhKJQdNV0naQ5FUA5bKimX20bqpjUVMCgZF7RpskSDkVo0XDJWZfwUvV59p3k7QrvGMKgp2FGHg_Laqn9vnO3VZ79TDa2JkGU2eHk0CP7bnONVo40GhkE78HNUVHBJSc35grIVNfnzMUB3_0xJ1DJqdXOl_h91Vr34u8N7ze_ZZoCvwN4POcj4dZj3EFQPekj9Lz9RS1pQQktSE0mKXGGM_QT5Mrn5</recordid><startdate>20210709</startdate><enddate>20210709</enddate><creator>Sugimoto, Atsunori</creator><creator>Suzuki, Yutaro</creator><creator>Orime, Naoki</creator><creator>Hayashi, Taketsugu</creator><creator>Yoshinaga, Kiyohiro</creator><creator>Egawa, Jun</creator><creator>Ono, Shin</creator><creator>Sugai, Takuro</creator><creator>Inoue, Yoshimasa</creator><creator>Someya, Toshiyuki</creator><general>Lippincott Williams & Wilkins</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6684-0016</orcidid></search><sort><creationdate>20210709</creationdate><title>The lowest effective plasma concentration of atomoxetine in pediatric patients with attention deficit/hyperactivity disorder: A non-randomized prospective interventional study</title><author>Sugimoto, Atsunori ; Suzuki, Yutaro ; Orime, Naoki ; Hayashi, Taketsugu ; Yoshinaga, Kiyohiro ; Egawa, Jun ; Ono, Shin ; Sugai, Takuro ; Inoue, Yoshimasa ; Someya, Toshiyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3553-40265c2e1f2cff92536524eb29249b89a8dc6e3e1345288553aec9a5849336253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adrenergic Uptake Inhibitors - pharmacokinetics</topic><topic>Atomoxetine Hydrochloride - pharmacokinetics</topic><topic>Attention Deficit Disorder with Hyperactivity - blood</topic><topic>Attention Deficit Disorder with Hyperactivity - drug therapy</topic><topic>Child</topic><topic>Clinical Trial/Experimental Study</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Prospective Studies</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sugimoto, Atsunori</creatorcontrib><creatorcontrib>Suzuki, Yutaro</creatorcontrib><creatorcontrib>Orime, Naoki</creatorcontrib><creatorcontrib>Hayashi, Taketsugu</creatorcontrib><creatorcontrib>Yoshinaga, Kiyohiro</creatorcontrib><creatorcontrib>Egawa, Jun</creatorcontrib><creatorcontrib>Ono, Shin</creatorcontrib><creatorcontrib>Sugai, Takuro</creatorcontrib><creatorcontrib>Inoue, Yoshimasa</creatorcontrib><creatorcontrib>Someya, Toshiyuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Medicine (Baltimore)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sugimoto, Atsunori</au><au>Suzuki, Yutaro</au><au>Orime, Naoki</au><au>Hayashi, Taketsugu</au><au>Yoshinaga, Kiyohiro</au><au>Egawa, Jun</au><au>Ono, Shin</au><au>Sugai, Takuro</au><au>Inoue, Yoshimasa</au><au>Someya, Toshiyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The lowest effective plasma concentration of atomoxetine in pediatric patients with attention deficit/hyperactivity disorder: A non-randomized prospective interventional study</atitle><jtitle>Medicine (Baltimore)</jtitle><addtitle>Medicine (Baltimore)</addtitle><date>2021-07-09</date><risdate>2021</risdate><volume>100</volume><issue>27</issue><spage>e26552</spage><epage>e26552</epage><pages>e26552-e26552</pages><issn>0025-7974</issn><eissn>1536-5964</eissn><abstract>Atomoxetine (ATX) is used as a first-line, non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD), although no studies have systematically examined the relationship between plasma concentration and clinical efficacy. We conducted this non-randomized prospective interventional study to examine the relationship between plasma concentration of ATX and clinical efficacy.
Forty-three ADHD pediatric patients received ATX, and the steady-state through plasma concentration of the last daily dose that was maintained for at least 4 weeks were determined by high-performance liquid chromatography.
The receiver operating characteristic curve suggested that when plasma concentration exceeded 64.60 ng/mL, scores on the ADHD-Rating Scale improved by 50% or more (P = .14). Although 6 of the 8 final responders were unresponsive at the initial dose (.72 ± .04 mg/kg [mean ± standard deviation]), they responded after increasing the ATX dose to the final dose (1.52 ± .31 mg/kg). Excluding 7 outlier participants, the concentration was 83.3 ± 32.3 ng/mL in 7 responders and was significantly higher than 29.5 ± 23.9 ng/mL (P < .01) for the 29 non-responders.
These results suggest that a minimum effective plasma concentration of ATX is required to achieve sufficient clinical efficacy. We hypothesized a mechanism that results in the realization of a clinical effect when the plasma concentration exceeds a certain threshold in the potential response group, whereas will not improve even if the plasma concentration is increased in the unqualified non-responder group.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins</pub><pmid>34232195</pmid><doi>10.1097/MD.0000000000026552</doi><orcidid>https://orcid.org/0000-0002-6684-0016</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Medicine (Baltimore), 2021-07, Vol.100 (27), p.e26552-e26552 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wolters Kluwer Open Health; IngentaConnect Free/Open Access Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adrenergic Uptake Inhibitors - pharmacokinetics Atomoxetine Hydrochloride - pharmacokinetics Attention Deficit Disorder with Hyperactivity - blood Attention Deficit Disorder with Hyperactivity - drug therapy Child Clinical Trial/Experimental Study Double-Blind Method Female Humans Male Prospective Studies Treatment Outcome |
| title | The lowest effective plasma concentration of atomoxetine in pediatric patients with attention deficit/hyperactivity disorder: A non-randomized prospective interventional study |
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