{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:24:15Z","timestamp":1791930255337,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>6\u2010Mercaptopurine (6MP) is the mainstay chemotherapy for acute lymphoblastic leukemia (ALL) and is conventionally available as 50\u00a0mg tablets. A new 6MP powder for oral suspension (PFOS 10\u00a0mg\/mL) was developed recently by IDRS Labs, India, intended for pediatric use. A comparative pharmacokinetics of PFOS with T. mercaptopurine was conducted to determine the dose equivalence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An open\u2010label, randomized, two\u2010treatment, two\u2010period, two\u2010sequence, single oral dose, crossover, bioequivalence study was conducted on 51 healthy adult subjects. Post hoc, a population pharmacokinetic (PopPK) model was developed using the healthy volunteer data to perform simulations with various PFOS doses and select a bioequivalent dose. Further, to confirm the safety of PFOS in pediatrics, a simulation of 6MP and 6\u2010thioguanine exposures was performed by incorporating the formulation\u2010specific parameters derived from the healthy volunteer study into the PopPK model in childhood ALL available in literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 6MP PFOS had 47% higher oral bioavailability compared to the reference product. Simulations using a two\u2010compartmental PopPK model with dissolution and transit compartments showed that 40\u00a0mg of PFOS was found to be equivalent to 50\u00a0mg tablets. The simulated 6\u2010thioguanine nucleotide concentrations in children using the dose adjusted for PFOS were between 114 and 703.6\u00a0pmol\/8\u00a0\u00d7\u00a010<jats:sup>8<\/jats:sup> RBC, which was within the range reported in pediatric ALL studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>6MP PFOS 10\u00a0mg\/mL should be administered at a 20% lower dose than the tablet to achieve comparable exposure. 6MP PFOS addresses an unmet medical need for a liquid formulation of 6MP in the Indian subcontinent.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.30813","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T07:38:53Z","timestamp":1702971533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bioequivalence study followed by model\u2010informed dose optimization of a powder for oral suspension of 6\u2010mercaptopurine"],"prefix":"10.1002","volume":"71","author":[{"given":"Bhavatharini","family":"Arun","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre  Navi Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendra","family":"Joshi","sequence":"additional","affiliation":[{"name":"IDRS Labs Pvt Ltd.  Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana Khosa","family":"Kakkar","sequence":"additional","affiliation":[{"name":"IDRS Labs Pvt Ltd.  Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivkumar","family":"Madki","sequence":"additional","affiliation":[{"name":"IDRS Labs Pvt Ltd.  Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Ivaturi","sequence":"additional","affiliation":[{"name":"Pumas AI, Inc.  Centreville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish","family":"Chinnaswamy","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai Maharashtra India"},{"name":"Homi Bhabha National Institute, Anushakthinagar  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shripad","family":"Banavali","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai Maharashtra India"},{"name":"Homi Bhabha National Institute, Anushakthinagar  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6348-6667","authenticated-orcid":false,"given":"Vikram","family":"Gota","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre  Navi Mumbai Maharashtra India"},{"name":"Homi Bhabha National Institute, Anushakthinagar  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"StatPearls","author":"Sharma H","year":"2022"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010022\u201001591\u20104"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000206"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010008\u20100478\u20106"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198304283081705"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V122.21.59.59"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2010.03867.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.10.3569"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011423663"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1715163518767942"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1185\/146300907X167817"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2008.03281.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2001.00366.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0928\u20100987(99)00027\u20105"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/PGPM.S288988"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.0245"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14258"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26139"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403783"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26465"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010020\u201004097\u2010x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011423663"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010021\u201001045\u20107"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.831"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1078155215577808"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.30813","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T13:05:16Z","timestamp":1713877516000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.30813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,18]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/pbc.30813"],"URL":"https:\/\/doi.org\/10.1002\/pbc.30813","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,18]]},"assertion":[{"value":"2023-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e30813"}}