{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:12:40Z","timestamp":1772118760612,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK081406"],"award-info":[{"award-number":["DK081406"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Previous reports have questioned the safety of multiple doses of acetaminophen administered to ill children. Acetaminophen protein adducts (adducts) are a biomarker of acetaminophen\u2010induced liver injury and reflect the oxidative metabolism of acetaminophen, a known mechanism in acetaminophen toxicity. In this prospective observational study, we analyzed adduct concentrations in 1034 blood samples obtained from 181 hospitalized children (1 to 18\u00a0years inclusive) who received 2 or more doses of acetaminophen. Linear regression analysis showed that serum adduct concentrations increased as a function of the cumulative acetaminophen dose, which could be attributed, in part, to a long half\u2010life of adducts (2.17\u00a0\u00b1\u00a01.04\u00a0days [mean\u00a0\u00b1\u00a0standard deviation]) in children. However, few patients (2%) were found to have adduct concentrations higher than 1.0\u00a0nmol\/mL, a previously identified toxicity cut point for the diagnosis of acetaminophen\u2010induced liver injury in patients with alanine aminotransferase values exceeding 1000\u00a0IU\/L. A small cohort of patients with suspected infection was noted to show higher adduct concentrations. In addition, adduct concentrations showed a stronger correlation with cumulative acetaminophen doses in adolescents compared with children (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.41 vs 0.26). No other covariates (body weight, body mass index\n                    <jats:italic>z<\/jats:italic>\n                    score, sex, race, or surgery) remarkably correlated with adduct elevation. In summary, low levels of adducts can be detected in hospitalized children receiving multiple doses of acetaminophen, and adduct levels correlate with cumulative acetaminophen dose.\n                  <\/jats:p>","DOI":"10.1002\/jcph.1442","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T05:11:14Z","timestamp":1558069874000},"page":"1291-1299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Acetaminophen Protein Adducts in Hospitalized Children Receiving Multiple Doses of Acetaminophen"],"prefix":"10.1002","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6444-5576","authenticated-orcid":false,"given":"Sibo","family":"Jiang","sequence":"first","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology Department of Pharmaceutics University of Florida  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2636-1889","authenticated-orcid":false,"given":"Valvanera","family":"Vozmediano","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology Department of Pharmaceutics University of Florida  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5815-2029","authenticated-orcid":false,"given":"Susan M.","family":"Abdel\u2010Rahman","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Medical Toxicology Children's Mercy Hospitals and Clinics  Kansas City MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4998-1167","authenticated-orcid":false,"given":"Stephan","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology Department of Pharmaceutics University of Florida  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4266-3924","authenticated-orcid":false,"given":"Laura P.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute  Little Rock AR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.108.4.1020"},{"key":"e_1_2_10_3_1","unstructured":"US Food and Drug Administration (FDA).Acetaminophen: Avoiding Liver Injury.2009.https:\/\/www.fda.gov\/ForConsumers\/ConsumerUpdates\/ucm168830.htm. 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