{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:38:13Z","timestamp":1783075093469,"version":"3.54.6"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>Apixaban is an oral direct inhibitor of factor Xa (FXa) that could be a treatment option for thromboembolism prevention in children with congenital or acquired heart disease (CAHD). Data from SAXOPHONE, a phase II pediatric study, were used to update a previously developed population pharmacokinetics (PPK) model and to assess the covariate effect of patient type on PK parameters while retaining previous covariates. Stochastic simulations were performed to assess whether the proposed dosing regimens in pediatric patients aged 28\u2009days to &lt;\u200918\u2009years matched adult exposures. The relationship between anti\u2010Factor Xa (AXA) and apixaban concentration, as well as apixaban concentration and chromogenic FX, were evaluated. Apixaban dose adjustment in response to the growth of pediatric patients and changes in age and weight were also assessed. Apixaban PK in pediatric patients with CAHD was well characterized by a 2\u2010compartment model with first\u2010order absorption, dose\u2010dependent F1, and first\u2010order elimination. Apixaban apparent clearance (CL\/F) and apparent volume of distribution in the central compartment (Vc\/F) increased with increasing body weight. Apixaban CL\/F was lower in pediatric patients with CAHD compared to adults and other pediatric patients. The fixed dose by weight\u2010tiered dosing regimen for pediatric patients with CAHD (28\u2009days to &lt;\u200918\u2009years) achieved target exposures similar to adult VTE treatment and nonvalvular atrial fibrillation populations. A linear PK\/PD relationship between apixaban and AXA was observed. Inhibition of FXa was observed across weight tiers. Apixaban dose adjustment in response to weight gain resulted in exposures similar to target adult exposures.<\/jats:p>","DOI":"10.1002\/cpt.3689","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T04:05:57Z","timestamp":1750737957000},"page":"365-377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of Apixaban Pharmacokinetics\/Pharmacodynamics and Dose Assessment in Pediatric Patients with Congenital or Acquired Heart Disease"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0690-5989","authenticated-orcid":false,"given":"Antoinette","family":"Ajavon\u2010Hartmann","sequence":"first","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6922-2483","authenticated-orcid":false,"given":"Praneeth","family":"Jarugula","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunmoon","family":"Back","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obinna","family":"Obianom","sequence":"additional","affiliation":[{"name":"Cognigen, Simulations Plus  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3301-0059","authenticated-orcid":false,"given":"Elizabeth","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Cognigen, Simulations Plus  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Crevar","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Marchisin","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton Pike New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Chen","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"He","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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