{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:59:49Z","timestamp":1788188389593,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["Grant decision 325667, 2019"],"award-info":[{"award-number":["Grant decision 325667, 2019"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007788","name":"Blood Disease Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007788","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["8037"],"award-info":[{"award-number":["8037"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Ibrutinib is used in the treatment of certain B\u2010cell malignancies. Due to its CYP3A4\u2010mediated metabolism and highly variable pharmacokinetics, it is prone to potentially harmful drug\u2010drug interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a randomized, placebo\u2010controlled, three\u2010phase crossover study, we examined the effect of the CYP3A4\u2010inhibiting antifungal posaconazole on ibrutinib pharmacokinetics. Eleven healthy participants ingested repeated doses of 300\u2009mg of posaconazole either in the morning or in the evening, or placebo. A single dose of ibrutinib (30, 70 or 140\u2009mg, respectively) was administered at 9\u00a0AM, 1 or 12\u2009h after the preceding posaconazole\/placebo dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      On average, morning posaconazole increased the dose\u2010adjusted geometric mean area under the plasma concentration\u2010time curve from zero to infinity (AUC\n                      <jats:sub>0\u2010\u221e<\/jats:sub>\n                      ) and peak plasma concentration (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) of ibrutinib 9.5\u2010fold (90% confidence interval [CI] 6.3\u201014.3,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and 8.5\u2010fold (90% CI 5.7\u201012.8,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), respectively, while evening posaconazole increased those 10.3\u2010fold (90% CI 6.7\u201016.0,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and 8.2\u2010fold (90% CI 5.2\u201013.2,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), respectively. Posaconazole had no significant effect on the half\u2010life of ibrutinib, but substantially reduced the metabolite PCI\u201045227 to ibrutinib AUC\n                      <jats:sub>0\u2010\u221e<\/jats:sub>\n                      ratio. There were no significant differences in ibrutinib pharmacokinetics between morning and evening posaconazole phases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Posaconazole increases ibrutinib exposure substantially, by about 10\u2010fold. This interaction cannot be avoided by dosing the drugs 12\u2009h apart. In general, a 70\u2010mg daily dose of ibrutinib should not be exceeded during posaconazole treatment to avoid potentially toxic systemic ibrutinib concentrations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.15932","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T22:06:21Z","timestamp":1698098781000},"page":"557-567","source":"Crossref","is-referenced-by-count":6,"title":["Posaconazole\u2010ibrutinib interaction cannot be avoided by staggered dosing: How to optimize ibrutinib dose during posaconazole treatment"],"prefix":"10.1111","volume":"90","author":[{"given":"Aleksi M.","family":"Olkkola","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuija","family":"Tapaninen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Department of Clinical Pharmacology, HUS Diagnostic Center Helsinki University Hospital  Helsinki Finland"},{"name":"Department of Hematology Helsinki University Hospital Comprehensive Cancer Center  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5713-5692","authenticated-orcid":false,"given":"Aleksi","family":"Tornio","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Faculty of Medicine University of Turku  Turku Finland"},{"name":"Unit of Clinical Pharmacology Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milka","family":"Hauta\u2010aho","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Department of Clinical Pharmacology, HUS Diagnostic Center Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"Lapatto\u2010Reiniluoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Department of Clinical Pharmacology, HUS Diagnostic Center Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Neuvonen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna I.","family":"Kiiski","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pertti J.","family":"Neuvonen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-2189","authenticated-orcid":false,"given":"Mikko","family":"Niemi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Department of Clinical Pharmacology, HUS Diagnostic Center Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-2788","authenticated-orcid":false,"given":"Janne T.","family":"Backman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Department of Clinical Pharmacology, HUS Diagnostic Center Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Janssen Biotech Inc.Imbruvica Prescribing Information. Accessed February 5 2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/217003s000lbl.pdf"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400376"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509388"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201019\u20102856"},{"key":"e_1_2_10_6_1","unstructured":"European public assessment report for Imbruvica. Accessed February 5 2023.https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/imbruvica"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010020\u201000870\u2010w"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.182907"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2998"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.060061"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.156"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12716"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1460474"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010015\u20102708\u20109"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201011\u2010818286"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy175"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010019\u20100388\u2010x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201012\u2010823393"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky286"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010017\u20103196\u20102"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061094"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010014\u20102617\u20103"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15542"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2009.02.022"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2012.639360"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12668"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.60"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009\u20109236(98)90165\u20105"},{"key":"e_1_2_10_29_1","unstructured":"Merck Sharp & Dohme Ltd.Noxafil Prescribing Information. Accessed May 29 2022.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/214770s000 205053s012 205596s012lbl.pdf"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010020\u201001306\u2010y"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/myc.13001"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab1026"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/2767\u20109764.CRC\u201021\u20100076"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13623"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15590"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18712"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018028761"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.049210"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15932","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T03:19:27Z","timestamp":1706584767000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.15932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,13]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/bcp.15932"],"URL":"https:\/\/doi.org\/10.1111\/bcp.15932","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,13]]}}}