{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:01Z","timestamp":1786978021726,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T00:00:00Z","timestamp":1545177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011096","name":"Jazz Pharmaceuticals, Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011096","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kimberly Brooks"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CPX\u2010351, a dual\u2010drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio, is approved in the United States for adults with newly diagnosed therapy\u2010related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia\u2010related changes. Population pharmacokinetics analyses were performed using nonlinear mixed\u2010effect modeling on pooled data from 3 clinical studies, and the impact of CPX\u2010351 exposures on efficacy and safety was assessed. The pharmacokinetics of cytarabine and daunorubicin were described using 2\u2010compartment models with linear elimination. None of the evaluated covariates had a clinically significant impact on plasma exposure to total cytarabine or daunorubicin, while bilirubin and formulation showed statistically significant effects on pharmacokinetic parameters of cytarabine and daunorubicin, respectively. In patients with mild\/moderate renal impairment or serum bilirubin \u22643\u00a0mg\/dL, plasma exposures to cytarabine and daunorubicin following CPX\u2010351 were within the variability range for patients with normal kidney function or serum bilirubin levels. Exposure\u2010response analysis demonstrated that better efficacy outcomes were associated with higher CPX\u2010351 exposure quartiles. Early mortality rates in all CPX\u2010351 exposure quartiles were lower vs the 7\u00a0+\u00a03 control group, and lower mortality rates were associated with higher exposure quartiles. A trend toward greater frequency of grade 3 treatment\u2010emergent adverse events (but not grade 4\/5 events) was observed at higher CPX\u2010351 exposure quartiles. Overall, the population pharmacokinetic analyses indicate no adjustments to the recommended dose and schedule of CPX\u2010351 are warranted for patients with mild\/moderate renal impairment or serum bilirubin \u22643\u00a0mg\/dL. Results from the exposure\u2010response analyses suggest the current CPX\u2010351 regimen provides a favorable risk\u2010benefit profile.<\/jats:p>","DOI":"10.1002\/jcph.1366","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T10:24:00Z","timestamp":1545215040000},"page":"748-762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Population Pharmacokinetics and Exposure\u2010Response Analyses for CPX\u2010351 in Patients With Hematologic Malignancies"],"prefix":"10.1002","volume":"59","author":[{"given":"Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Jazz Pharmaceuticals, Inc.  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamalika","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals, Inc.  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grygoriy","family":"Vasilinin","sequence":"additional","affiliation":[{"name":"Certara  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.F.","family":"Marier","sequence":"additional","affiliation":[{"name":"Certara  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Gibbons","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals, Inc.  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-209262"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.60.0890"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V58.6.1203.1203"},{"issue":"4","key":"e_1_2_9_5_1","first-page":"485","article-title":"Cytosine arabinoside (NSC\u201063878) and daunorubicin (NSC\u201083142) therapy in acute nonlymphocytic leukemia","volume":"57","author":"Yates JW","year":"1973","journal-title":"Cancer Chemother Rep"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-301713"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403187"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2010.01.015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2008.06.028"},{"key":"e_1_2_9_10_1","unstructured":"VYXEOS\u2122 (daunorubicin and cytarabine injection) solution for intravenous use [package insert]. Palo Alto CA; Jazz Pharmaceuticals Inc.; 2017."},{"issue":"1","key":"e_1_2_9_11_1","first-page":"34","article-title":"Nanoscale complexes. A novel nanotechnology\u2010based platform to optimize combination cancer therapies: rational development & improved delivery using CombiPlex\u00ae","volume":"16","author":"Liboiron BD","year":"2016","journal-title":"Drug Dev Delivery."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-06-0118"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.5961"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-540971"},{"key":"e_1_2_9_15_1","unstructured":"LancetJE UyGL CortesJE et\u00a0al.Final results of a phase III randomized trial of CPX\u2010351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting; June 3\u20107 2016; Chicago IL."},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","unstructured":"LancetJE HoeringA UyGL et\u00a0al.Survival following allogeneic hematopoietic cell transplantation in older high\u2010risk acute myeloid leukemia patients initially treated with CPX\u2010351 liposome injection versus standard cytarabine and daunorubicin: subgroup analysis of a large phase III trial. Presented at the American Society of Hematology Annual Meeting & Exposition; December 3\u20136 2016; San Diego CA.","DOI":"10.1182\/blood.V128.22.906.906"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2012.07.006"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.2510.2510"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-017-3484-5"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2012.4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-009-9112-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-19425-7"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-011-1800-z"},{"key":"e_1_2_9_24_1","unstructured":"Daunorubicin. Daunorubicin hyrdochloride injection [package insert]. Bedford OH: Bedford Laboratories; 2013."},{"key":"e_1_2_9_25_1","unstructured":"Cytarabine. Cytarabine injection [package insert]. Montr\u00e9al Qu\u00e9bec: Hospira Healthcare Corporation; 2014."},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.143180"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T02:09:53Z","timestamp":1694225393000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,19]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/jcph.1366"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1366","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,19]]},"assertion":[{"value":"2018-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}