{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:10:41Z","timestamp":1768281041128,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"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":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Graft\u2010versus\u2010host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug\u2010drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics.<\/jats:p><jats:p>This study aimed to assess the impact of inflammation, as indicated by C\u2010reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no\u2010to\u2010mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration\/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration\/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation.<\/jats:p><jats:p>The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.<\/jats:p>","DOI":"10.1002\/jcph.6141","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T15:22:35Z","timestamp":1728487355000},"page":"328-339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-852X","authenticated-orcid":false,"given":"David","family":"Malno\u00eb","sequence":"first","affiliation":[{"name":"Centre Hospitalier Universitaire de Rennes P\u00f4le Pharmacie Secteur Pharmacotechnie et Onco\u2010Pharmacie  Rennes France"},{"name":"Facult\u00e9 de Pharmacie Laboratoire de Biopharmacie et Pharmacie Clinique, Universit\u00e9 de Rennes  Rennes France"},{"name":"Inserm, EHESP Institut de recherche en sant\u00e9 environnement et travail (IRSET) \u2010UMR_S 1085, Universit\u00e9 Rennes  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Bories","sequence":"additional","affiliation":[{"name":"CHU Rennes, INSERM LTSI\u2010UMR 1099, Universit\u00e9 de Rennes  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgane","family":"Pierre\u2010Jean","sequence":"additional","affiliation":[{"name":"CHU Rennes, INSERM LTSI\u2010UMR 1099, Universit\u00e9 de Rennes  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Marchand","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Clinique CHU de Rennes, INSERM U1236, Universit\u00e9 de Rennes  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4483-0957","authenticated-orcid":false,"given":"Pascal","family":"Le Corre","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Rennes P\u00f4le Pharmacie Secteur Pharmacotechnie et Onco\u2010Pharmacie  Rennes France"},{"name":"Facult\u00e9 de Pharmacie Laboratoire de Biopharmacie et Pharmacie Clinique, Universit\u00e9 de Rennes  Rennes France"},{"name":"Inserm, EHESP Institut de recherche en sant\u00e9 environnement et travail (IRSET) \u2010UMR_S 1085, Universit\u00e9 Rennes  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20103026(19)30256\u2010X"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010004\u20109004\u20104"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0169\u2010409x(97)00043\u20104"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010015\u20100339\u20102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552\u20104604.1990.tb01868.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010013\u20100037\u2010x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1991.tb03906.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1083\u20108791(03)00076\u20104"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.22037\/ijpr.2020.112111.13539"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2432"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.82"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03820\u201014"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.13569"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010022\u201003378\u2010z"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2020.1768381"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.25011\/cim.v41i1.29458"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01489\u201012"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2009.38"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12016"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4103\/jrpp.JRPP_16_163"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.12751"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/24.5.781"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890\u2010199604270\u201000026"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/10781552211029046"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010007\u20100395\u20100"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010013\u20109500\u20108"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.807"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.337"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.399"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.59"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009\u20109236(95)90067\u20105"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.05.020"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10081798"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2021.1928791"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.6141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T08:10:39Z","timestamp":1741767039000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.6141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,9]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/jcph.6141"],"URL":"https:\/\/doi.org\/10.1002\/jcph.6141","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,9]]},"assertion":[{"value":"2024-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}