{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:24:31Z","timestamp":1791221071856,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":1588,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p><jats:bold>Study Objective<\/jats:bold>. To evaluate the single\u2010 and multiple\u2010dose pharmacokinetics of an oral extended\u2010release formulation of guanfacine in children and adolescents with a diagnosis of attention\u2010deficit\u2013hyperactivity disorder (ADHD).<\/jats:p><jats:p><jats:bold>Design<\/jats:bold>. Phase I\u2010II, open\u2010label, dose\u2010escalation study.<\/jats:p><jats:p><jats:bold>Setting<\/jats:bold>. Clinical study center.<\/jats:p><jats:p><jats:bold>Patients<\/jats:bold>. Fourteen children (aged 6\u201312 yrs) and 14 adolescents (aged 13\u201317 yrs) with ADHD.<\/jats:p><jats:p><jats:bold>Intervention<\/jats:bold>. All patients received guanfacine as a single 2\u2010mg dose on day 1. They received a daily dose of 2 mg on days 9\u201315, 3 mg on days 16\u201322, and 4 mg on days 23\u201329.<\/jats:p><jats:p><jats:bold>Measurements and Main Results<\/jats:bold>. Blood samples, vital signs, and electrocardiograms (ECGs) were obtained before dosing on day 1 and at intervals over 24 hours, with repeat measurements on days 14 and 28. Guanfacine demonstrated linear pharmacokinetics. Mean plasma concentrations, peak exposure (C<jats:sub>max<\/jats:sub>), and total or 24\u2010hour exposure (area under the concentration\u2010time curve [AUC]<jats:sub>0\u2013\u221e<\/jats:sub> or AUC<jats:sub>0\u201324<\/jats:sub>, respectively) were as follows in children and adolescents, respectively: after a single 2\u2010mg dose, AUC<jats:sub>0\u2013\u221e<\/jats:sub> was 65.2 \u00b1 23.9 ng\u2022hour\/ml and 47.3 \u00b1 13.7 ng\u2022hour\/ml, and C<jats:sub>max<\/jats:sub> was 2.55 \u00b1 1.03 ng\/ml and 1.69 \u00b1 0.43 ng\/ml; after multiple 2\u2010mg doses, AUC<jats:sub>0\u201324<\/jats:sub> was 70.0 \u00b1 28.3 ng\u2022hour\/ml and 48.2 \u00b1 16.1 ng\u2022hour\/ml, and C<jats:sub>max<\/jats:sub> was 4.39 \u00b1 1.66 ng\/ml and 2.86 \u00b1 0.77 ng\/ml; and after multiple 4\u2010mg doses, AUC<jats:sub>0\u201324<\/jats:sub> was 162 \u00b1 116 ng\u2022hour\/ml and 117 \u00b1 28.4 ng\u2022hour\/ml, and C<jats:sub>max<\/jats:sub> was 10.1 \u00b1 7.09 ng\/ml and 7.01 \u00b1 1.53 ng\/ml. After a single 2\u2010mg dose, half\u2010life was 14.4 \u00b1 2.39 hours in children and 17.9 \u00b1 5.77 hours in adolescents. The most frequent treatment\u2010emergent adverse events were somnolence, insomnia, headache, blurred vision, and altered mood. Most were mild to moderate in severity, with the highest frequency associated with the 4\u2010mg doses. Blood pressure, pulse, and ECG readings were all within normal limits.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>. Guanfacine extended\u2010release formulation demonstrated linear pharmacokinetics. Plasma concentrations and concentration\u2010related pharmacokinetic parameters were higher in children than in adolescents. These differences are likely due to heavier body weights in adolescents and young male subjects. No serious adverse events were reported.<\/jats:p>","DOI":"10.1592\/phco.27.9.1253","type":"journal-article","created":{"date-parts":[[2007,8,27]],"date-time":"2007-08-27T09:07:06Z","timestamp":1188205626000},"page":"1253-1262","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Pharmacokinetics of a Guanfacine Extended\u2010Release Formulation in Children and Adolescents with Attention\u2010Deficit\u2013Hyperactivity Disorder"],"prefix":"10.1002","volume":"27","author":[{"given":"Samuel W.","family":"Boellner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pennick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Fiske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Shojaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.8.1025"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.157.1.17"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199509000-00010"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/cap.1995.5.215"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199501000-00013"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-200104000-00015"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.7.1067"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1996.01830050084013"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(99)00070-6"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(00)00111-1"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/8.3.269"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2999977"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050533"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-3955(05)70064-X"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-11-04287.1988"},{"key":"e_1_2_1_17_2","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association.","year":"2005"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.27.9.1253","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.27.9.1253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:05:59Z","timestamp":1761051959000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.27.9.1253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9]]},"references-count":16,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2007,9]]}},"alternative-id":["10.1592\/phco.27.9.1253"],"URL":"https:\/\/doi.org\/10.1592\/phco.27.9.1253","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9]]},"assertion":[{"value":"2012-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}