{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:10:55Z","timestamp":1778929855528,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009975","name":"Charotar University of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009975","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Tacrolimus (Tac or FK\u2010506) is an immunosuppressive agent that inhibits T\u2010cell activation and proliferation. It has a narrow therapeutic index and shows inter\u2010patient variabilities in its plasma concentration. Human Leucocyte Antigen (HLA) plays a major role in immune regulation and function. Tac inhibits the T\u2010cells, and\n                      <jats:italic>HLA<\/jats:italic>\n                      antigens are expressed in T\u2010cells. The objective of this study was to determine the role of the\n                      <jats:italic>HLA<\/jats:italic>\n                      Class I (\n                      <jats:italic>HLA\u2010A, HLA\u2010B,<\/jats:italic>\n                      and\n                      <jats:italic>HLA\u2010C<\/jats:italic>\n                      ) and Class II (\n                      <jats:italic>HLA\u2010DRB1, HLA\u2010DQB1,<\/jats:italic>\n                      and\n                      <jats:italic>HLA\u2010DQA1<\/jats:italic>\n                      ) in influencing Tac PK among renal transplant patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      This study included\n                      <jats:italic>HLA<\/jats:italic>\n                      genotyping data of 462 renal transplant patients. Tacrolimus blood trough concentration\/dose (Co\/D) was calculated on day 7 and months 1, 3, 6, and 12 post\u2010transplantation, and the association with\n                      <jats:italic>HLA<\/jats:italic>\n                      alleles was studied. Furthermore, biopsy\u2010proven toxicity, rejection, and pathological events were evaluated for their association with\n                      <jats:italic>HLA<\/jats:italic>\n                      alleles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      One\u2010way ANOVA analysis showed that\n                      <jats:italic>HLA\u2010B*51:01<\/jats:italic>\n                      and\n                      <jats:italic>HLA\u2010C*16:02<\/jats:italic>\n                      were significantly associated with Tac Co\/D at multiple time points, with a significance level of\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05. In addition,\n                      <jats:italic>HLA\u2010DRB1*04:03<\/jats:italic>\n                      was associated with post\u2010renal transplant toxicity [Hazard Ratio (HR)\u2009=\u20098.500, 95% Confidential Interval (CI) (1.517\u201347.619)] and pathological events [HR\u2009=\u20092.310, 95% CI (1.149\u20134.642)].\n                      <jats:italic>HLA\u2010A*02:11<\/jats:italic>\n                      [HR\u2009=\u20093.530, 95% CI (1.074\u201311.601)], and\n                      <jats:italic>HLA\u2010DQB*03:01<\/jats:italic>\n                      [HR\u2009=\u20095.055, 95% CI (1.544\u201316.551)] were associated with high risk of transplant rejection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our data suggest that\n                      <jats:italic>HLA<\/jats:italic>\n                      alleles influence the PK of Tac and affect graft survival in renal transplant patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.70141","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T07:19:26Z","timestamp":1775632766000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Human Leucocyte Antigen with Tacrolimus Pharmacokinetics in Renal Transplant Patients"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-6831","authenticated-orcid":false,"given":"Rashmi J.","family":"Hemani","sequence":"first","affiliation":[{"name":"Department of Pathology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"},{"name":"Department of Pharmacology, Ramanbhai Patel College of Pharmacy Charotar University of Science and Technology (CHARUSAT)  Changa Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit S.","family":"Joreja","sequence":"additional","affiliation":[{"name":"Department of Pathology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nitiraj B.","family":"Shete","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratika","family":"Srivastava","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Department of Biotechnology Babasaheb Bhimrao Ambedkar University (A Central University)  Lucknow UP India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailesh M.","family":"Soni","sequence":"additional","affiliation":[{"name":"Department of Pathology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shishir D.","family":"Gang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhijit M.","family":"konnur","sequence":"additional","affiliation":[{"name":"Department of Nephrology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umapati N.","family":"Hegde","sequence":"additional","affiliation":[{"name":"Department of Nephrology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hardik B.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Nephrology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banibrata N.","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Pathology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manan A.","family":"Raval","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Phytochemistry, Ramanbhai Patel College of Pharmacy Charotar University of Science and Technology (CHARUSAT)  Changa Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0567-5344","authenticated-orcid":false,"given":"Sachchida Nand","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Pathology Muljibhai Patel Urological Hospital  Nadiad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1489"},{"key":"e_1_2_10_3_1","first-page":"179","article-title":"The Major Histocompatibility Complex and Autoimmunity","volume":"3","author":"Chaplin D. D.","year":"1988","journal-title":"Year in Immunology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.143"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/kisup.2011.14"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.4c00055"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/aor.13551"},{"issue":"4","key":"e_1_2_10_8_1","first-page":"275","article-title":"A Systematic Review and Meta\u2010Analysis Recite the Efficacy of Tacrolimus Treatment in Renal Transplant Patients in Association With Genetic Variants of CYP3A5 Gene","volume":"11","author":"Chauhan P. M.","year":"2023","journal-title":"Am J Clin Exp Urol"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i48.9156"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1517\/phgs.4.4.397.22747"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.109"},{"key":"e_1_2_10_12_1","first-page":"115","article-title":"Clinical and genetic determinants of tacrolimus pharmacokinetics and pharmacodynamics in the transplant population","author":"Kirresh T.","year":"2014","journal-title":"ProQuest Diss Theses"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199512000-00007"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/15.12.1916"},{"issue":"3","key":"e_1_2_10_15_1","first-page":"133","article-title":"The Roles of CD4 and CD8 in T Cell Activation","volume":"3","author":"Miceli M. C. J. R.","year":"1991","journal-title":"Seminars in Immunology"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.7.2945"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.9.3686"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JHEP.2022.09.010"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14903.Allopurinol"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13250"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31258.HLA\u2010B"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15898"},{"key":"e_1_2_10_23_1","volume-title":"Heptinstall's Pathology of the Kidney","author":"Charles Jennette J.","year":"2023"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.726784"},{"issue":"1","key":"e_1_2_10_25_1","first-page":"506","article-title":"Epidemiology of Severe Cutaneous Adverse Drug Reaction and Its HLA Association Among Pediatrics","volume":"18","author":"Esmaeilzadeh H.","year":"2019","journal-title":"Iran J Pharm Res"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1706"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.14.135"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2016.61"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.08.004"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1248386"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijmy.ijmy_143_18"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13566"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2024.100901"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201005\u2010086934"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000248"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2217\/PGS.13.180"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397\u2010019\u20100121\u20101"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2016.42"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2013.04.020"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1086\/378097"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.70141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/phar.70141","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.70141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T10:40:45Z","timestamp":1778928045000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.70141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/phar.70141"],"URL":"https:\/\/doi.org\/10.1002\/phar.70141","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]},"assertion":[{"value":"2025-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70141"}}