{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:43:11Z","timestamp":1791297791376,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T00:00:00Z","timestamp":1334620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan as add\u2010on therapy or transition from bosentan. Safety included evaluation of adverse events including aminotransferase abnormalities. The clinical impact was evaluated by improvement from baseline in clinical variables. A total of 38 pediatric patients with PAH received ambrisentan. Fifteen of 38 patients were switched from bosentan to ambrisentan. The remaining 23 children were treated with ambrisentan as an add\u2010on therapy due to disease progression. In both transition and add\u2010on cases, mean pulmonary artery pressure significantly improved (transition; 55\u2009\u00b1\u200918 vs. 45\u2009\u00b1\u200920\u2009mmHg, n\u2009=\u200913,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.04, add\u2010on; 52\u2009\u00b1\u200917 vs. 45\u2009\u00b1\u200919\u2009mmHg, n\u2009=\u200913,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.03) during the follow\u2010up. World Health Organization functional class improved in 31% of patients, but one patient required an atrial septostomy due to disease progression during the follow\u2010up period (median, range; 20, 4\u201344 months). Five patients (13%) discontinued ambrisentan due to severe headache, lack of clinical efficacy, or near syncope. Ten patients (26%) had side effects associated with ambrisentan treatment, including nasal congestion, headache, and flushing. However, no patients had aminotransferase abnormalities and there were no deaths after initiation of ambrisentan during follow\u2010up. Pharmacokinetics were evaluated in sixteen children treated with ambrisentan from 2.5\u2009mg to 10.0\u2009mg; the mean peak plasma concentration was 738\u2009\u00b1\u2009452\u2009ng\/ml, mean time to peak plasma concentration was 3.2\u2009\u00b1\u20092.1 hours, and mean area under the curve plasma concentration was 6657\u2009\u00b1\u20094246\u2009ng\u00b7hour\/ml. In conclusion, initial experience with ambrisentan in children suggests that treatment is safe with similar pharmacokinetics to those in adults and may improve PAH in some children. Pediatr Pulmonol. 2013; 48:27\u201334. \u00a9 2012 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ppul.22555","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T08:45:16Z","timestamp":1334652316000},"page":"27-34","source":"Crossref","is-referenced-by-count":91,"title":["Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension"],"prefix":"10.1002","volume":"48","author":[{"given":"Shinichi","family":"Takatsuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika B.","family":"Rosenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Zuckerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Brady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Calderbank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Dunbar","family":"Ivy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,17]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199306173282402"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.042"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.11.026"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90387-5"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.1.114"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656560903061275"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2010.12.051"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-0574"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2009.09.008"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.742510"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012212"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn234"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.04.050"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0408-z"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008315315"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008324180"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200443150-00003"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2009.03532.x"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.2217\/14796678.1.4.425"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2009.03384.x"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fppul.22555","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.22555","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T08:00:45Z","timestamp":1696665645000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.22555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,17]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["10.1002\/ppul.22555"],"URL":"https:\/\/doi.org\/10.1002\/ppul.22555","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4,17]]}}}