{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:55Z","timestamp":1786977955317,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The absorption and bioavailability of most tyrosine kinase inhibitors are affected by gastrointestinal pH as they are weak basic lipophilic drugs. Hence, concomitant use of acid reducing agents (ARAs) is frequently restricted. Particularly comedication of crystalline dasatinib (Sprycel) and proton\u2010pump inhibitors (PPIs) should be avoided. Drug\u2013drug interaction (DDI) studies with PPIs report approximately 40%\u201080% bioavailability reduction of dasatinib. Limitations in the design of these studies do not allow for assessing the near maximum DDI as timing of PPI dosing was either not reported or 22 h prior to dasatinib intake. We conducted a DDI study of crystalline dasatinib and omeprazole in healthy, fasted participants, investigating the impact of PPI comedication on dasatinib plasma exposure at a time point when the near maximum DDI effect is expected. Participants were administered omeprazole (day 2\u20105) to reach steady state. On day 6, a single dose of crystalline dasatinib was given. Crystalline dasatinib dosing alone on day 1 served as control (single dose). The dosing interval between omeprazole administration and crystalline dasatinib was 10 h (median [range: 9\u201010 h]). Dasatinib C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u201024<\/jats:sub>\n                    were reduced by 96% and 89% by omeprazole comedication. C\n                    <jats:sub>max<\/jats:sub>\n                    was 224.6 \u00b1 104.7 ng\/mL (mean \u00b1 SD) and 8.0 \u00b1 4.5 ng\/mL (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;\u00a0.0001) and AUC\n                    <jats:sub>0\u201024<\/jats:sub>\n                    was 797.6 \u00b1 274.5 and 90.6 \u00b1 38.1 h\u00b7ng\/mL (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;\u00a0.0001) without and with omeprazole. T\n                    <jats:sub>1\/2<\/jats:sub>\n                    was 5.7 \u00b1 1.5 h (mean \u00b1 SD) with crystalline dasatinib dosing alone and could not be reliably calculated with comedication. To ensure optimal patient outcome, it is vital to investigate bioavailability of pH\u2010sensitive drugs at the maximal DDI effect of ARAs to understand the worst\u2010case influence for efficient clinical management.\n                  <\/jats:p>","DOI":"10.1002\/jcph.6173","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T01:38:28Z","timestamp":1735263508000},"page":"588-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Severe Impact of Omeprazole Timing on pH\u2010Sensitive Dasatinib Absorption: Unveiling Substantial Drug\u2013Drug Interaction"],"prefix":"10.1002","volume":"65","author":[{"given":"Per","family":"Andersson","sequence":"first","affiliation":[{"name":"Xspray Pharma  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9415-1750","authenticated-orcid":false,"given":"Magnus","family":"Brisander","sequence":"additional","affiliation":[{"name":"Xspray Pharma  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotta","family":"Liljebris","sequence":"additional","affiliation":[{"name":"Xspray Pharma  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rald","family":"Jesson","sequence":"additional","affiliation":[{"name":"Xspray Pharma  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1578-5184","authenticated-orcid":false,"given":"Hans","family":"Lennern\u00e4s","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010024\u201000939\u20101"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13146"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106774"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2007.04.002"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw019"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094\u2010012\u20100767\u20105"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102010\u201007\u2010294330"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/cad.0000000000001356"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.73"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009333854"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.2165\/11207580\u2010000000000\u201000000"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/290159a0"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmacy6020043"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1010"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894\u2010008\u20100098\u20104"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl15502"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102036.2004.02140.x"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102036.2000.00813.x"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185\u2010020\u201002845\u20106"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010015\u20101968\u2010y"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/cpaa.S42796"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/ftd.0000000000000639"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010014\u20109673\u20109"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010011\u20101797\u20103"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12895"},{"key":"e_1_2_14_27_1","unstructured":"EMA.Sprycel (dasatinib) product information. 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