{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:51:57Z","timestamp":1786978317240,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n Treatment for pediatric acute lymphoblastic leukemia includes asparaginase as an integral component of therapy. Hypersensitivity reactions or silent inactivation to\n \n Escherichia coli<\/jats:italic>\n <\/jats:styled-content>\n (\n \n E. coli<\/jats:styled-content>\n )\n <\/jats:italic>\n formulations may necessitate switching to\n Erwinia<\/jats:italic>\n \u2010based asparaginase (asparaginase\n \n Erwinia chrysanthemi<\/jats:italic>\n <\/jats:styled-content>\n [E\u2010ASP] or recombinant asparaginase\n \n Erwinia chrysanthemi<\/jats:italic>\n <\/jats:styled-content>\n [R\u2010ASP]). However, pharmacokinetic data for R\u2010ASP in pediatrics remain\u00a0limited, and recommended dosing schedules present logistical challenges. We investigated if adherence to approved dosing regimens for R\u2010ASP is necessary to achieve optimal pharmacokinetic exposure in pediatric patients with leukemia or lymphoma.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We performed a single institution, retrospective review of pharmacokinetic data in patients who received R\u2010ASP between October 1, 2021 and September 30, 2024. A one\u2010compartment pharmacokinetic model with first\u2010order absorption and elimination was used to evaluate asparaginase pharmacokinetic activity. The pharmacokinetic model was used to determine if the labeled dosing window for R\u2010ASP is required to achieve effective asparagine depletion.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Twenty\u2010six patients with 115 measurements of serum asparaginase activity (SAA) were included in the analysis.\u2009Based on model simulations from our pediatric patient data, maintaining SAA \u2265\u20090.1\u2009IU\/mL in 90% of patients throughout the dosing interval with R\u2010ASP 25\/25\/50\u2009mg\/m\n 2<\/jats:sup>\n administered intramuscularly on Monday, Wednesday, and Friday requires precise timing. Specifically, the Friday 50\u2009mg\/m\n 2<\/jats:sup>\n dose must be administered within 58\u2009h of the Wednesday morning dose to sustain therapeutic activity. Additionally, only 62.5% of patients maintained SAA \u2265\u20090.1\u2009IU\/mL at 72\u2009h after the last dose with R\u2010ASP 25\u2009mg\/m\n 2<\/jats:sup>\n administered intramuscularly on a Monday, Wednesday, and Friday dosing schedule.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Overall, our findings support the importance of adhering closely to the United States Food and Drug Administration approved dosing schedule for R\u2010ASP to ensure adequate asparaginase activity in pediatric patients with leukemia or lymphoma.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/phar.70146","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:15:06Z","timestamp":1776759306000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Dosing Interval Adherence on Pharmacokinetic Outcomes of Recombinant\n Erwinia<\/i>\n Asparaginase in Pediatric Leukemia or Lymphoma"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-8267","authenticated-orcid":false,"given":"Milre M.","family":"Matherne","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1308-7208","authenticated-orcid":false,"given":"John C.","family":"Panetta","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn","family":"Hopp","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0605-7342","authenticated-orcid":false,"given":"Hiroto","family":"Inaba","sequence":"additional","affiliation":[{"name":"Department of Oncology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0303-5658","authenticated-orcid":false,"given":"Ching\u2010Hon","family":"Pui","sequence":"additional","affiliation":[{"name":"Department of Oncology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8113-8180","authenticated-orcid":false,"given":"Seth E.","family":"Karol","sequence":"additional","affiliation":[{"name":"Department of Oncology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-3624","authenticated-orcid":false,"given":"M. Brooke","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2490-9655","authenticated-orcid":false,"given":"Hope D.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.137380"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102013\u201001\u2010480822"},{"key":"e_1_2_11_4_1","unstructured":"Pharmaceuticals J \u201cRylaze \u201d(2022)."},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12947"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13499"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016923"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024013346"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000030"},{"issue":"24","key":"e_1_2_11_11_1","first-page":"6568","article-title":"Measurement of Serum L\u2010Asparagine in the Presence of L\u2010Asparaginase Requires the Presence of an L\u2010Asparaginase Inhibitor","volume":"51","author":"Asselin B.","year":"1991","journal-title":"Cancer Research"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1542146"},{"issue":"11","key":"e_1_2_11_13_1","first-page":"4554","article-title":"L\u2010Asparaginase Pharmacokinetics and Asparagine Levels in Cerebrospinal Fluid of Rhesus Monkeys and Humans","volume":"41","author":"Riccardi R.","year":"1981","journal-title":"Cancer Research"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008368916800"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.206433"},{"issue":"1","key":"e_1_2_11_16_1","first-page":"24","article-title":"A Pharmacological Study on Pegylated Asparaginase Used in Front\u2010Line Treatment of Children With Acute Lymphoblastic Leukemia","volume":"91","author":"Rizzari C.","year":"2006","journal-title":"Haematologica"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01464.x"},{"issue":"7","key":"e_1_2_11_18_1","first-page":"478","article-title":"High\u2010Throughput Asparaginase Activity Assay in Serum of Children With Leukemia","volume":"6","author":"Fu C.\u2010A.","year":"2013","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.18.02439"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1012299115260"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.70146","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/phar.70146","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.70146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T10:40:15Z","timestamp":1778928015000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.70146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/phar.70146"],"URL":"https:\/\/doi.org\/10.1002\/phar.70146","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"assertion":[{"value":"2025-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70146"}}