{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:19:53Z","timestamp":1787822393321,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are widely used in patients with cystic fibrosis and significantly improve respiratory function and quality of life. However, their effectiveness may be limited by liver damage, which sometimes leads to treatment discontinuation, and the mechanisms underlying this remain poorly understood. This case series explores the role of genetic polymorphisms affecting the enzymes and transporters involved in their pharmacokinetics, as well as detoxification mechanisms (CYP3A4\/CYP3A5\/ABCB1\/SLCO1B1\/GSTP1\/GSTM1\/GSTT1). Six cases of hepatotoxicity under CFTR modulators were assessed using the RECAM score. Among the genetic polymorphisms assessed,\n                    <jats:italic>CYP3A4*22<\/jats:italic>\n                    (rs35599367) allele had higher allele frequency than in the European population, which usually does not express CYP3A5. This genetic variant, reducing CYP3A activity, could decrease the elimination of CFTR modulators and increase the risk of liver toxicity. Other genetic factors may also be involved. Further studies are needed to confirm these results.\n                  <\/jats:p>","DOI":"10.1002\/bcp.70660","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:23:56Z","timestamp":1782393836000},"page":"3257-3264","source":"Crossref","is-referenced-by-count":0,"title":["A descriptive case series of hepatotoxicity associated with CFTR modulators and possible relevance of pharmacogenetic polymorphisms in cystic fibrosis patients"],"prefix":"10.1002","volume":"92","author":[{"given":"Clara","family":"Laffitte Redondo","sequence":"first","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique et Pharmacog\u00e9nomique CHU Kremlin Bic\u00eatre, APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venceslas","family":"Bourdin","sequence":"additional","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance, Service de Pharmacologie, H\u00f4pital Cochin, AP\u2010HP, Universit\u00e9 de Paris; R\u00e9seau Fran\u00e7ais de Pharmacovigilance  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abd El Kader","family":"Ait Tayeb","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique et Pharmacog\u00e9nomique CHU Kremlin Bic\u00eatre, APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihem","family":"Benaboud","sequence":"additional","affiliation":[{"name":"Service de Pharmacologie Clinique H\u00f4pital Cochin, AP\u2010HP, Universit\u00e9 de Paris\u2010Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Martins","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique et Pharmacog\u00e9nomique CHU Kremlin Bic\u00eatre, APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Joyau","sequence":"additional","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance, Service de Pharmacologie Clinique, Institut de Biologie CHU H\u00f4tel Dieu  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Benhamida","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tence pour la Mucoviscidose H\u00f4pital M\u00e8re\u2010Enfant  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Sermet\u2010Gaudelus","sequence":"additional","affiliation":[{"name":"INSERM U1151, Universit\u00e9 Paris Cit\u00e9, H\u00f4pital Necker Enfants Malades, APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Martin","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Cit\u00e9, Inserm U1016  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre R\u00e9gis","family":"Burgel","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Cit\u00e9, Inserm U1016  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Verstuyft","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique et Pharmacog\u00e9nomique CHU Kremlin Bic\u00eatre, APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-3571","authenticated-orcid":false,"given":"Laurent","family":"Chouchana","sequence":"additional","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance, Service de Pharmacologie, H\u00f4pital Cochin, AP\u2010HP, Universit\u00e9 de Paris; R\u00e9seau Fran\u00e7ais de Pharmacovigilance  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9 Inserm UMR\u2010S 1343, Pharmacologie et \u00e9valuations des th\u00e9rapeutiques chez l'enfant et la femme enceinte  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-3803","authenticated-orcid":false,"given":"Estelle","family":"Ayme\u2010Dietrich","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique et Pharmacog\u00e9nomique CHU Kremlin Bic\u00eatre, APHP  Paris France"},{"name":"Laboratoire de Pharmacologie et Toxicologie NeuroCardiovasculaire, UR7296, H\u00f4pitaux Universitaires de Strasbourg Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14124335"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010025\u201001516\u20101"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.02.013"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/life15081256"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010023\u201001969\u20103"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.07.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.70073"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22370"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010025\u201001507\u20102"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2023.2220960"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32327"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151696"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0895\u20104356(00)00314\u20100"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678\u20104685\u2010GMB\u20102016\u20100142"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000090753.99170.89"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2010.28"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12038"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13103"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01104\u201022"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010014\u20101703\u20100"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/14622416.2024.2346069"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.10.004"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.27473"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2024.2426616"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920009790711805"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v32.i10.114946"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2013.10.002"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.03.003"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.13815"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.11.011"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.16191"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70660","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70660","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70660","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:38:32Z","timestamp":1787819912000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":31,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/bcp.70660"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70660","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}