{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:36:40Z","timestamp":1753893400876,"version":"3.41.2"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Transpl Int"],"abstract":"<jats:p>Solid organ transplant recipients are at an increased risk of developing skin cancers due to chronic immunosuppression, particularly with calcineurin inhibitors. Tacrolimus is the most prescribed calcineurin inhibitor in this patient cohort, and understanding tacrolimus concentrations in the skin will facilitate the development of anti-cancer preventive and therapeutic strategies. Here, we show that in mice, tacrolimus blood levels peaked rapidly \u223c1\u00a0h post last oral dose while skin levels rose more slowly and remained high for at least 6\u00a0h. Subsequently, tacrolimus skin and blood concentrations were assessed in 15 kidney transplant recipients. The mean age was 61\u00a0years, the average time post-transplant was 7\u00a0years (range 0\u201321\u00a0years) and 87% were male. The average skin sampling time post tacrolimus dosing was 6\u00a0h 32\u00a0min. Skin tacrolimus concentrations ranged from 7.1\u00a0ng\/g to 71.2\u00a0ng\/g and correlated with blood concentrations (r = 0.6). Mouse and human mean skin concentrations were in a similar range. Our data suggests that tacrolimus measurements in the blood may be used to approximate tacrolimus concentrations in the skin of kidney transplant recipients, and further exploited for the delivery of anti-cancer therapies designed to antagonize the immunosuppressive effects of tacrolimus in the skin.<\/jats:p>","DOI":"10.3389\/ti.2024.12019","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T04:11:28Z","timestamp":1705983088000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting Tacrolimus Concentrations in the Skin of Adult Kidney Transplant Recipients: A Feasibility Study"],"prefix":"10.3389","volume":"37","author":[{"given":"Felicity","family":"Sartain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea K.","family":"Viecelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Veitch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian W.","family":"Dymock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott B.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1111\/ajt.14382","article-title":"Skin Cancers in Organ Transplant Recipients","volume":"17","author":"Mittal","year":"2017","journal-title":"Am J Transpl"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1056\/NEJMra022137","article-title":"Skin Cancers After Organ Transplantation","volume":"348","author":"Euvrard","year":"2003","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/ijc.29450","article-title":"Does the Nature of Residual Immune Function Explain the Differential Risk of Non-Melanoma Skin Cancer Development in Immunosuppressed Organ Transplant Recipients?","volume":"138","author":"Jung","year":"2016","journal-title":"Int J Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s40620-014-0098-4","article-title":"Skin Cancer in Kidney Transplant Recipients","volume":"27","author":"Ponticelli","year":"2014","journal-title":"J Nephrol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1056\/NEJMoa1204166","article-title":"Sirolimus and Secondary Skin-Cancer Prevention in Kidney Transplantation","volume":"367","author":"Euvrard","year":"2012","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1111\/nep.13939","article-title":"Reducing Non-Melanoma Skin Cancer Risk in Renal Transplant Recipients","volume":"26","author":"Thet","year":"2021","journal-title":"Nephrology (Carlton)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1200\/JCO.1995.13.8.1933","article-title":"Prevention of Skin Cancer and Reduction of Keratotic Skin Lesions During Acitretin Therapy in Renal Transplant Recipients: A Double-Blind, Placebo-Controlled Study","volume":"13","author":"Bavinck","year":"1995","journal-title":"J Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1056\/NEJMoa1506197","article-title":"A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention","volume":"373","author":"Chen","year":"2015","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1111\/j.1600-6143.2012.04004.x","article-title":"Randomized Controlled Trial of Sirolimus for Renal Transplant Recipients at High Risk for Nonmelanoma Skin Cancer","volume":"12","author":"Campbell","year":"2012","journal-title":"Am J Transpl"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1111\/bcp.13367","article-title":"NFAT-Regulated Cytokine Gene Expression During Tacrolimus Therapy Early After Renal Transplantation","volume":"83","author":"Bremer","year":"2017","journal-title":"Br J Clin Pharmacol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.3390\/cancers13092131","article-title":"IFN-Gamma Critically Enables the Intratumoural Infiltration of CXCR3(+) CD8(+) T Cells to Drive Squamous Cell Carcinoma Regression","volume":"13","author":"Zeng","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1600-0625.2011.01413.x","article-title":"Skin Cancer in Organ Transplant Recipients: Effects of Immunosuppressive Medications on DNA Repair","volume":"21","author":"Kuschal","year":"2012","journal-title":"Exp Dermatol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e006783","DOI":"10.1136\/jitc-2023-006783","article-title":"Local Blockade of Tacrolimus Promotes T-Cell-Mediated Tumor Regression in Systemically Immunosuppressed Hosts","volume":"11","author":"Veitch","year":"2023","journal-title":"J ImmunoTherapy Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e171","DOI":"10.1097\/TXD.0000000000000694","article-title":"Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients","volume":"3","author":"Burke","year":"2017","journal-title":"Transpl Direct"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e1479627","DOI":"10.1080\/2162402X.2018.1479627","article-title":"Clinically-Relevant Rapamycin Treatment Regimens Enhance CD8(+) Effector Memory T Cell Function in the Skin and Allow Their Infiltration Into Cutaneous Squamous Cell Carcinoma","volume":"7","author":"Jung","year":"2018","journal-title":"Oncoimmunology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3390\/pharmaceutics11080394","article-title":"Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels","volume":"11","author":"Rancan","year":"2019","journal-title":"Pharmaceutics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.0022-202X.2005.23644.x","article-title":"A Multicenter Study of the Pharmacokinetics of Tacrolimus Ointment After First and Repeated Application to Children With Atopic Dermatitis","volume":"124","author":"Harper","year":"2005","journal-title":"J Invest Dermatol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/j.jaad.2022.02.039","article-title":"Chemoprevention of Cutaneous Squamous Cell Carcinoma and its Precursors in Solid Organ Transplant Recipients Using Topical Sirolimus: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial","volume":"87","author":"Chong","year":"2022","journal-title":"J Am Acad Dermatol"}],"container-title":["Transplant International"],"original-title":[],"link":[{"URL":"https:\/\/www.frontierspartnerships.org\/articles\/10.3389\/ti.2024.12019\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T04:11:30Z","timestamp":1705983090000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontierspartnerships.org\/articles\/10.3389\/ti.2024.12019\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,23]]},"references-count":18,"alternative-id":["10.3389\/ti.2024.12019"],"URL":"https:\/\/doi.org\/10.3389\/ti.2024.12019","relation":{},"ISSN":["1432-2277"],"issn-type":[{"type":"electronic","value":"1432-2277"}],"subject":[],"published":{"date-parts":[[2024,1,23]]},"article-number":"12019"}}