{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T04:09:20Z","timestamp":1780805360877,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T00:00:00Z","timestamp":1499990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      The CYP3A metric 4\u03b2\u2010hydroxycholesterol (4\u03b2OHC) has been shown to correlate with tacrolimus steady\u2010state apparent oral clearance (CL\/F). Recently, pretransplant 4\u03b2OHC was shown not to predict tacrolimus CL\/F after transplantation in a cohort of renal recipients (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a079). The goal of the current study was determine whether these findings could be validated in a substantially larger cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a retrospective analysis of 279 renal recipients, tacrolimus trough concentrations (C0), daily dose, haematocrit and other relevant covariates were registered every day for the first 14 days after transplantation. 4\u03b2OHC and cholesterol were quantified on plasma collected immediately pretransplant using liquid chromatography tandem\u2010mass spectrometry. Patients were genotyped for\n                      <jats:italic>CYP3A5*1<\/jats:italic>\n                      and\n                      <jats:italic>CYP3A4*22<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 3551 tacrolimus C0 concentrations were registered. In a linear mixed model for the 14\u2010day period, determinants of tacrolimus C0 were CYP3A5 genotype, haematocrit, age and weight (overall\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.179). Determinants of daily dose were CYP3A5 genotype, age, methylprednisolone dose, tacrolimus formulation, ALT and estimated glomerular filtration rate (overall\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.242). Considering each of the first 5 days separately, 4\u03b2OHC had a limited effect on tacrolimus C0 on day 3 only (\u22121.00\u00a0ng\u00a0ml\n                      <jats:sup>\u22121<\/jats:sup>\n                      per ln,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.035) but not on any other day, and no effect on dose or C0\/dose. During the first 5 days, haematocrit and age, which were previously established as determinants of tacrolimus disposition under steady\u2010state conditions, never explained more than 17.7% of between\u2010subject variability in tacrolimus C0\/dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The CYP3A metric 4\u03b2OHC cannot be used to predict tacrolimus dose requirements in the first days after transplantation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.13343","type":"journal-article","created":{"date-parts":[[2017,6,11]],"date-time":"2017-06-11T21:56:39Z","timestamp":1497218199000},"page":"2406-2415","source":"Crossref","is-referenced-by-count":14,"title":["Pretransplant 4\u03b2\u2010hydroxycholesterol does not predict tacrolimus exposure or dose requirements during the first days after kidney transplantation"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-6294","authenticated-orcid":false,"given":"Thomas","family":"Vanhove","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology KU Leuven \u2013 University of Leuven  Leuven Belgium"},{"name":"Department of Nephrology and Renal Transplantation University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Center of Drug Absorption and Transport (C_DAT) University Hospital Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven \u2013 University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Oswald","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Center of Drug Absorption and Transport (C_DAT) University Hospital Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk R. J.","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology KU Leuven \u2013 University of Leuven  Leuven Belgium"},{"name":"Department of Nephrology and Renal Transplantation University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13355"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/11317550-000000000-00000"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.13.133"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13691"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.109"},{"key":"e_1_2_10_9_1","first-page":"1","article-title":"Clinical determinants of calcineurin inhibitor disposition: a mechanistic review","volume":"2532","author":"Vanhove T","year":"2016","journal-title":"Drug Metab Rev"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.11.90"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13059"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90177-0"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105127200"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03309.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201712200"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13083"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13248"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000305"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2016.08.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P040022"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000708"},{"key":"e_1_2_10_24_1","unstructured":"International HapMap Project [Internet]. 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