{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T09:02:31Z","timestamp":1793523751975,"version":"4.5.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100007543","name":"Agence Nationale de S\u00e9curit\u00e9 du M\u00e9dicament et des Produits de Sant\u00e9","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007543","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["CAPTOR PHUC-001"],"award-info":[{"award-number":["CAPTOR PHUC-001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","award":["C15092BS"],"award-info":[{"award-number":["C15092BS"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1007\/s40262-020-00884-0","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T22:07:46Z","timestamp":1587679666000},"page":"1171-1183","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Population Pharmacokinetics of Ibrutinib and Its Dihydrodiol Metabolite in Patients with Lymphoid Malignancies"],"prefix":"10.1007","volume":"59","author":[{"given":"Fanny","family":"Gallais","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Ysebaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Despas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"De Barros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Dupr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Quillet-Mary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Protin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Ob\u00e9ric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Allal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Chatelut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"White-Koning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"issue":"12","key":"884_CR1","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1517\/14656566.2015.1067302","volume":"16","author":"MR Smith","year":"2015","unstructured":"Smith MR. Ibrutinib in B lymphoid malignancies. Expert Opin Pharmacother. 2015;16(12):1879\u201387.","journal-title":"Expert Opin Pharmacother."},{"issue":"29","key":"884_CR2","doi-asserted-by":"publisher","first-page":"13075","DOI":"10.1073\/pnas.1004594107","volume":"107","author":"LA Honigberg","year":"2010","unstructured":"Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA. 2010;107(29):13075\u201380.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"12","key":"884_CR3","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1038\/nri955","volume":"2","author":"H Niiro","year":"2002","unstructured":"Niiro H, Clark EA. Regulation of B-cell fate by antigen-receptor signals. Nat Rev Immunol. 2002;2(12):945\u201356.","journal-title":"Nat Rev Immunol."},{"issue":"6","key":"884_CR4","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1182\/blood-2012-02-362624","volume":"120","author":"JA Woyach","year":"2012","unstructured":"Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood. 2012;120(6):1175\u201384.","journal-title":"Blood."},{"issue":"1","key":"884_CR5","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1056\/NEJMoa1215637","volume":"369","author":"JC Byrd","year":"2013","unstructured":"Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32\u201342.","journal-title":"N Engl J Med."},{"issue":"5","key":"884_CR6","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1182\/blood-2011-10-386417","volume":"119","author":"S Ponader","year":"2012","unstructured":"Ponader S, Chen S-S, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012;119(5):1182\u20139.","journal-title":"Blood."},{"issue":"11","key":"884_CR7","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1182\/blood-2011-11-390989","volume":"119","author":"MFM de Rooij","year":"2012","unstructured":"de Rooij MFM, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590\u20134.","journal-title":"Blood."},{"issue":"2","key":"884_CR8","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1124\/dmd.114.060061","volume":"43","author":"E Scheers","year":"2015","unstructured":"Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, et al. Absorption, metabolism, and excretion of oral 14C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos Biol Fate Chem. 2015;43(2):289\u201397.","journal-title":"Drug Metab Dispos Biol Fate Chem."},{"issue":"4","key":"884_CR9","doi-asserted-by":"publisher","first-page":"e00156","DOI":"10.1002\/prp2.156","volume":"3","author":"J de Jong","year":"2015","unstructured":"de Jong J, Skee D, Murphy J, Sukbuntherng J, Hellemans P, Smit J, et al. Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants. Pharmacol Res Perspect. 2015;3(4):e00156.","journal-title":"Pharmacol Res Perspect."},{"key":"884_CR10","unstructured":"European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). 24 July 2014, EMA\/CHMP\/645137\/2014. https:\/\/www.ema.europa.eu\/documents\/assessment-report\/imbruvica-epar-public-assessment-report_en.pdf. Accessed 11 Mar 2020."},{"issue":"1","key":"884_CR11","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s00280-014-2617-3","volume":"75","author":"E Marostica","year":"2015","unstructured":"Marostica E, Sukbuntherng J, Loury D, de Jong J, de Trixhe XW, Vermeulen A, et al. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015;75(1):111\u201321.","journal-title":"Cancer Chemother Pharmacol."},{"issue":"1","key":"884_CR12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.2217\/pgs.12.187","volume":"14","author":"L Elens","year":"2013","unstructured":"Elens L, van Gelder T, Hesselink DA, Haufroid V, van Schaik RHN. CYP3A4*22: promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy. Pharmacogenomics. 2013;14(1):47\u201362.","journal-title":"Pharmacogenomics."},{"issue":"4","key":"884_CR13","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1517\/14622416.6.4.357","volume":"6","author":"S-J Lee","year":"2005","unstructured":"Lee S-J, Goldstein JA. Functionally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their detection with genotyping tests. Pharmacogenomics. 2005;6(4):357\u201371.","journal-title":"Pharmacogenomics."},{"issue":"6","key":"884_CR14","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1177\/0091270003253617","volume":"43","author":"CR Yates","year":"2003","unstructured":"Yates CR, Zhang W, Song P, Li S, Gaber AO, Kotb M, et al. The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients. J Clin Pharmacol. 2003;43(6):555\u201364.","journal-title":"J Clin Pharmacol."},{"issue":"4","key":"884_CR15","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/BF01060893","volume":"9","author":"LB Sheiner","year":"1981","unstructured":"Sheiner LB, Beal SL. Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm. 1981;9(4):503\u201312.","journal-title":"J Pharmacokinet Biopharm."},{"issue":"4","key":"884_CR16","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1002\/cpt.982","volume":"103","author":"PG Baverel","year":"2018","unstructured":"Baverel PG, Dubois VFS, Jin CY, Zheng Y, Song X, Jin X, et al. Population pharmacokinetics of durvalumab in cancer patients and association with longitudinal biomarkers of disease status. Clin Pharmacol Ther. 2018;103(4):631\u201342.","journal-title":"Clin Pharmacol Ther."},{"issue":"5","key":"884_CR17","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/clpt.2010.20","volume":"87","author":"A Lindauer","year":"2010","unstructured":"Lindauer A, Di Gion P, Kanefendt F, Tomalik-Scharte D, Kinzig M, Rodamer M, et al. Pharmacokinetic\/pharmacodynamic modeling of biomarker response to sunitinib in healthy volunteers. Clin Pharmacol Ther. 2010;87(5):601\u20138.","journal-title":"Clin Pharmacol Ther."},{"issue":"3","key":"884_CR18","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s40262-016-0443-y","volume":"56","author":"H Yu","year":"2017","unstructured":"Yu H, van Erp N, Bins S, Mathijssen RHJ, Schellens JHM, Beijnen JH, et al. Development of a pharmacokinetic model to describe the complex pharmacokinetics of pazopanib in cancer patients. Clin Pharmacokinet. 2017;56(3):293\u2013303.","journal-title":"Clin Pharmacokinet."},{"issue":"3","key":"884_CR19","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1111\/bcp.12388","volume":"78","author":"R ter Heine","year":"2014","unstructured":"ter Heine R, Binkhorst L, de Graan AJM, de Bruijn P, Beijnen JH, Mathijssen RHJ, et al. Population pharmacokinetic modelling to assess the impact of CYP2D6 and CYP3A metabolic phenotypes on the pharmacokinetics of tamoxifen and endoxifen. Br J Clin Pharmacol. 2014;78(3):572\u201386.","journal-title":"Br J Clin Pharmacol."},{"issue":"3","key":"884_CR20","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1208\/s12248-011-9282-9","volume":"13","author":"J Bertrand","year":"2011","unstructured":"Bertrand J, Laffont CM, Mentr\u00e9 F, Chenel M, Comets E. Development of a complex parent-metabolite joint population pharmacokinetic model. AAPS J. 2011;13(3):390\u2013404.","journal-title":"AAPS J."},{"issue":"6","key":"884_CR21","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1046\/j.1365-2125.2003.01967.x","volume":"56","author":"T Kerbusch","year":"2003","unstructured":"Kerbusch T, W\u00e4hlby U, Milligan PA, Karlsson MO. Population pharmacokinetic modelling of darifenacin and its hydroxylated metabolite using pooled data, incorporating saturable first-pass metabolism, CYP2D6 genotype and formulation-dependent bioavailability. Br J Clin Pharmacol. 2003;56(6):639\u201352.","journal-title":"Br J Clin Pharmacol."},{"issue":"4","key":"884_CR22","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/leu.2015.316","volume":"30","author":"S-S Chen","year":"2016","unstructured":"Chen S-S, Chang BY, Chang S, Tong T, Ham S, Sherry B, et al. BTK inhibition results in impaired CXCR4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia. Leukemia. 2016;30(4):833\u201343.","journal-title":"Leukemia."},{"issue":"8","key":"884_CR23","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1038\/leu.2016.129","volume":"30","author":"F Cervantes-Gomez","year":"2016","unstructured":"Cervantes-Gomez F, Kumar Patel V, Bose P, Keating MJ, Gandhi V. Decrease in total protein level of Bruton\u2019s tyrosine kinase during ibrutinib therapy in chronic lymphocytic leukemia lymphocytes. Leukemia. 2016;30(8):1803\u20134.","journal-title":"Leukemia."},{"issue":"21","key":"884_CR24","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1182\/blood-2018-06-860593","volume":"132","author":"LS Chen","year":"2018","unstructured":"Chen LS, Bose P, Cruz ND, Jiang Y, Wu Q, Thompson PA, et al. A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia. Blood. 2018;132(21):2249\u201359.","journal-title":"Blood."},{"issue":"2","key":"884_CR25","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1111\/bjh.14540","volume":"181","author":"AR Mato","year":"2018","unstructured":"Mato AR, Timlin C, Ujjani C, Skarbnik A, Howlett C, Banerjee R, et al. Comparable outcomes in chronic lymphocytic leukaemia (CLL) patients treated with reduced-dose ibrutinib: results from a multi-centre study. Br J Haematol. 2018;181(2):259\u201361.","journal-title":"Br J Haematol."},{"issue":"S2","key":"884_CR26","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/hon.2438_100","volume":"35","author":"GA Follows","year":"2017","unstructured":"Follows GA, Forum UKC. Outcomes of patients post ibrutinib treatment for relapsed\/refractory CLL: a UK and Ireland analysis. Hematol Oncol. 2017;35(S2):237\u20138.","journal-title":"Hematol Oncol."}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-020-00884-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-020-00884-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-020-00884-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T00:35:35Z","timestamp":1619310935000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-020-00884-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,24]]},"references-count":26,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["884"],"URL":"https:\/\/doi.org\/10.1007\/s40262-020-00884-0","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,24]]},"assertion":[{"value":"24 April 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"This study has been supported by the French National Drug Agency (ANSM), the French National Research Agency (ANR, project CAPTOR PHUC-001), and the AVIESAN, INCa and INSERM Plan Cancer program (project C15092BS).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Lo\u00efc Ysebaert received grant support and honorarium fees from Roche, Abbvie, Gilead and Janssen, but not in the scope of the present study. Lucie Ob\u00e9ric received honorarium fees from Roche and Janssen, but not in the scope of the present study. Fanny Gallais, Fabien Despas, Sandra De Barros, Lo\u00efc Dupr\u00e9, Anne Quillet-Mary, Caroline Protin, Fabienne Thomas, Ben Allal, Etienne Chatelut and M\u00e9lanie White-Koning have no conflicts of interest that are directly relevant to the content of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted in compliance with ethical standards.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"All patients gave their written informed consent.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}}]}}