{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:45:15Z","timestamp":1767771915901,"version":"3.37.3"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Drug Metab Pharmacokinet"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1007\/s13318-020-00644-2","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T09:02:43Z","timestamp":1599210163000},"page":"749-760","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combined Effect of Inter- and Intrapatient Variability in Tacrolimus Exposure on Graft Impairment Within a 3-Year Period Following Kidney Transplantation: A Single-Center Experience"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2599-7508","authenticated-orcid":false,"given":"Nikola Z.","family":"Stefanovi\u0107","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radmila M.","family":"Veli\u010dkovi\u0107-Radovanovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina S.","family":"Dankovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branka P.","family":"Miti\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goran J.","family":"Paunovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina B.","family":"Cvetkovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatjana P.","family":"Cvetkovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"issue":"2","key":"644_CR1","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.trre.2015.01.002","volume":"29","author":"N Shuker","year":"2015","unstructured":"Shuker N, van Gelder T, Hesselink DA. Intra-patient variability in tacrolimus exposure: causes, consequences for clinical management. Transplant Rev (Orlando). 2015;29(2):78\u201384.","journal-title":"Transplant Rev (Orlando)"},{"issue":"11","key":"644_CR2","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1111\/tri.12798","volume":"29","author":"N Shuker","year":"2016","unstructured":"Shuker N, Shuker L, van Rosmalen J, Roodnat JI, Borra LC, Weimar W, et al. A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation. Transpl Int. 2016;29(11):1158\u201367.","journal-title":"Transpl Int"},{"issue":"8","key":"644_CR3","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1093\/ndt\/gfq096","volume":"25","author":"LC Borra","year":"2010","unstructured":"Borra LC, Roodnat JI, Kal JA, Mathot RA, Weimar W, van Gelder T. High within-patient variability in the clearance of tacrolimus is a risk factor for poor long-term outcome after kidney transplantation. Nephrol Dial Transplant. 2010;25(8):2757\u201363.","journal-title":"Nephrol Dial Transplant"},{"issue":"11","key":"644_CR4","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1097\/TP.0000000000001040","volume":"100","author":"E Rodrigo","year":"2016","unstructured":"Rodrigo E, Segundo DS, Fern\u00e1ndez-Fresnedo G, L\u00f3pez-Hoyos M, Benito A, Ruiz JC, et al. Within-patient variability in tacrolimus blood levels predicts kidney graft loss and donor-specific antibody development. Transplantation. 2016;100(11):2479\u201385.","journal-title":"Transplantation"},{"issue":"5","key":"644_CR5","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1111\/ajt.15199","volume":"19","author":"AD Leino","year":"2019","unstructured":"Leino AD, King EC, Jiang W, Vinks AA, Klawitter J, Christians U, et al. Assessment of tacrolimus intrapatient variability in stable adherent transplant recipients: establishing baseline values. Am J Transplant. 2019;19(5):1410\u201320.","journal-title":"Am J Transplant"},{"issue":"2","key":"644_CR6","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/cpt.1618","volume":"107","author":"DRJ Kuypers","year":"2020","unstructured":"Kuypers DRJ. Intrapatient variability of tacrolimus exposure in solid organ transplantation: a novel marker for clinical outcome. Clin Pharmacol Ther. 2020;107(2):347\u201358.","journal-title":"Clin Pharmacol Ther"},{"issue":"8","key":"644_CR7","doi-asserted-by":"publisher","first-page":"e192","DOI":"10.1097\/TXD.0000000000000710","volume":"3","author":"DL Goodall","year":"2017","unstructured":"Goodall DL, Willicombe M, McLean AG, Taube D. High intrapatient variability of tacrolimus levels and outpatient clinic nonattendance are associated with inferior outcomes in renal transplant patients. Transplant Direct. 2017;3(8):e192.","journal-title":"Transplant Direct"},{"key":"644_CR8","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.biopha.2018.03.054","volume":"102","author":"X Zhang","year":"2018","unstructured":"Zhang X, Lin G, Tan L, Li J. Current progress of tacrolimus dosing in solid organ transplant recipients: pharmacogenetic considerations. Biomed Pharmacother. 2018;102:107\u201314.","journal-title":"Biomed Pharmacother"},{"issue":"11","key":"644_CR9","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1124\/dmd.118.081935","volume":"46","author":"T Vanhove","year":"2018","unstructured":"Vanhove T, de Jonge H, de Loor H, Oorts M, de Hoon J, Pohanka A, et al. Relationship between in vivo CYP3A4 activity, CYP3A5 genotype, and systemic tacrolimus metabolite\/parent drug ratio in renal transplant recipients and healthy volunteers. Drug Metab Dispos. 2018;46(11):1507\u201313.","journal-title":"Drug Metab Dispos"},{"issue":"6","key":"644_CR10","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1097\/TP.0000000000002920","volume":"104","author":"T Jouve","year":"2020","unstructured":"Jouve T, Fonrose X, Noble J, Janbon B, Fiard G, Malvezzi P, et al. The TOMATO study (Tacrolimus Metabolization in Kidney Transplantation): impact of the concentration\u2013dose ratio on death-censored graft survival. Transplantation. 2020;104(6):1263\u201371.","journal-title":"Transplantation"},{"issue":"7","key":"644_CR11","doi-asserted-by":"publisher","first-page":"E2193","DOI":"10.3390\/jcm9072193","volume":"9","author":"C Thongprayoon","year":"2020","unstructured":"Thongprayoon C, Hansrivijit P, Kovvuru K, Kanduri SR, Bathini T, Pivovarova A, et al. Impacts of high intra- and inter-individual variability in tacrolimus pharmacokinetics and fast tacrolimus metabolism on outcomes of solid organ transplant recipients. J Clin Med. 2020;9(7):E2193.","journal-title":"J Clin Med"},{"issue":"10","key":"644_CR12","doi-asserted-by":"publisher","first-page":"e111128","DOI":"10.1371\/journal.pone.0111128","volume":"9","author":"G Th\u00f6lking","year":"2014","unstructured":"Th\u00f6lking G, Fortmann C, Koch R, Gerth HU, Pabst D, Pavenst\u00e4dt H, et al. The tacrolimus metabolism rate influences renal function after kidney transplantation. PLoS ONE. 2014;9(10):e111128.","journal-title":"PLoS ONE"},{"issue":"4","key":"644_CR13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.7326\/0003-4819-145-4-200608150-00004","volume":"145","author":"AS Levey","year":"2006","unstructured":"Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4):247\u201354.","journal-title":"Ann Intern Med"},{"issue":"1","key":"644_CR14","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s12291-010-0085-z","volume":"26","author":"TF Ashavaid","year":"2011","unstructured":"Ashavaid TF, Raje HS, Shah BV, Shah SA. Design of allele specific PCR for rapid detection of CYP3A5 (A6986G) and Mdr-1 (C3435T) polymorphisms. Indian J Clin Biochem. 2011;26(1):18\u2013211.","journal-title":"Indian J Clin Biochem"},{"issue":"3","key":"644_CR15","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.3892\/etm.2015.2598","volume":"10","author":"NZ Stefanovi\u0107","year":"2015","unstructured":"Stefanovi\u0107 NZ, Cvetkovi\u0107 TP, Jevtovi\u0107-Stoimenov TM, Ignjatovi\u0107 AM, Paunovi\u0107 GJ, Veli\u010dkovi\u0107-Radovanovi\u0107 RM. Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: effects on tacrolimus exposure and kidney function. Exp Ther Med. 2015;10(3):1149\u201356.","journal-title":"Exp Ther Med"},{"key":"644_CR16","doi-asserted-by":"publisher","first-page":"439","DOI":"10.12659\/AOT.897938","volume":"21","author":"CH Baek","year":"2016","unstructured":"Baek CH, Kim H, Yang WS, Han DJ, Park SK. A postoperative 1-year eGFR of more than 45 ml\/min may be the cutoff level for a favorable long-term prognosis in renal transplant patients. Ann Transplant. 2016;21:439\u201347.","journal-title":"Ann Transplant"},{"issue":"2","key":"644_CR17","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1097\/TP.0000000000001129","volume":"101","author":"HR Whalen","year":"2017","unstructured":"Whalen HR, Glen JA, Harkins V, Stevens KK, Jardine AG, Geddes CC, et al. High intrapatient tacrolimus variability is associated with worse outcomes in renal transplantation using a low-dose tacrolimus immunosuppressive regime. Transplantation. 2017;101(2):430\u20136.","journal-title":"Transplantation"},{"issue":"5","key":"644_CR18","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3390\/jcm8050587","volume":"8","author":"K Sch\u00fctte-N\u00fctgen","year":"2019","unstructured":"Sch\u00fctte-N\u00fctgen K, Th\u00f6lking G, Steinke J, Pavenst\u00e4dt H, Schmidt R, Suwelack B, et al. Fast tacrolimus metabolizers at risk\u2014it is time for a C\/D ratio calculation. J Clin Med. 2019;8(5):587.","journal-title":"J Clin Med"},{"issue":"10","key":"644_CR19","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/j.1432-2277.2003.tb00230.x","volume":"16","author":"EM van Duijnhoven","year":"2003","unstructured":"van Duijnhoven EM, Boots JM, Christiaans MH, Stolk LM, Undre NA, van Hooff JP. Increase in tacrolimus trough levels after steroid withdrawal. Transpl Int. 2003;16(10):721\u20135.","journal-title":"Transpl Int"},{"issue":"12","key":"644_CR20","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1080\/1744666X.2020.1693263","volume":"15","author":"A Mendoza Rojas","year":"2019","unstructured":"Mendoza Rojas A, Hesselink DA, van Besouw NM, Baan CC, van Gelder T. Impact of low tacrolimus exposure and high tacrolimus intra-patient variability on the development of de novo anti-HLA donor-specific antibodies in kidney transplant recipients. Expert Rev Clin Immunol. 2019;15(12):1323\u201331.","journal-title":"Expert Rev Clin Immunol"},{"issue":"4","key":"644_CR21","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1742-7843.2012.00892.x","volume":"111","author":"IW Kim","year":"2012","unstructured":"Kim IW, Noh H, Ji E, Han N, Hong SH, Ha J, et al. Identification of factors affecting tacrolimus level and 5-year clinical outcome in kidney transplant patients. Basic Clin Pharmacol Toxicol. 2012;111(4):217\u201323.","journal-title":"Basic Clin Pharmacol Toxicol"},{"issue":"1","key":"644_CR22","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/cpdd.22","volume":"2","author":"SK Sy","year":"2013","unstructured":"Sy SK, Singh RP, Shilbayeh S, Zmeili R, Conrado D, Derendorf H. Influence of CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms on adverse events associated with tacrolimus in Jordanian pediatric renal transplant patients. Clin Pharmacol Drug Dev. 3435C;2(1):67\u201378.","journal-title":"Clin Pharmacol Drug Dev"},{"issue":"5","key":"644_CR23","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1517\/17425255.2016.1170808","volume":"12","author":"JT Tang","year":"2016","unstructured":"Tang JT, Andrews LM, van Gelder T, Shi YY, van Schaik RH, Wang LL, et al. Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations. Expert Opin Drug Metab Toxicol. 2016;12(5):555\u201365.","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"9","key":"644_CR24","doi-asserted-by":"publisher","first-page":"3046","DOI":"10.1093\/ndt\/gfr253","volume":"26","author":"F Glowacki","year":"2011","unstructured":"Glowacki F, Lionet A, Buob D, Labalette M, Allorge D, Prov\u00f4t F, et al. CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on tacrolimus dose requirements and clinical outcome after renal transplantation. Nephrol Dial Transplant. 2011;26(9):3046\u201350.","journal-title":"Nephrol Dial Transplant"},{"key":"644_CR25","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.intimp.2018.03.004","volume":"58","author":"N Komine","year":"2018","unstructured":"Komine N, Satoh S, Saito M, Numakura K, Inoue T, Tsuruta H, et al. Influence of CYP3A5 genetic differences in tacrolimus on quantitative interstitial fibrosis and long-term graft function in kidney transplant recipients. Int Immunopharmacol. 2018;58:57\u201363.","journal-title":"Int Immunopharmacol"},{"issue":"3","key":"644_CR26","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1097\/FTD.0b013e318289644d","volume":"35","author":"N Spierings","year":"2013","unstructured":"Spierings N, Holt DW, MacPhee IA. CYP3A5 genotype had no impact on intrapatient variability of tacrolimus clearance in renal transplant recipients. Ther Drug Monit. 2013;35(3):328\u201331.","journal-title":"Ther Drug Monit"},{"issue":"10","key":"644_CR27","doi-asserted-by":"publisher","first-page":"2954","DOI":"10.1111\/ajt.13803","volume":"16","author":"T Vanhove","year":"2016","unstructured":"Vanhove T, Vermeulen T, Annaert P, Lerut E, Kuypers DRJ. High intrapatient variability of tacrolimus concentrations predicts accelerated progression of chronic histologic lesions in renal recipients. Am J Transplant. 2016;16(10):2954\u201363.","journal-title":"Am J Transplant"},{"issue":"6","key":"644_CR28","doi-asserted-by":"publisher","first-page":"e455","DOI":"10.1097\/TXD.0000000000000899","volume":"5","author":"H Mo","year":"2019","unstructured":"Mo H, Kim SY, Min S, Han A, Ahn S, Min SK, et al. Association of intrapatient variability of tacrolimus concentration with early deterioration of chronic histologic lesions in kidney transplantation. Transplant Direct. 2019;5(6):e455.","journal-title":"Transplant Direct"},{"issue":"2","key":"644_CR29","first-page":"393","volume":"32","author":"B Rozen-Zvi","year":"2017","unstructured":"Rozen-Zvi B, Schneider S, Lichtenberg S, Green H, Cohen O, Gafter U, et al. Association of the combination of time-weighted variability of tacrolimus blood level and exposure to low drug levels with graft survival after kidney transplantation. Nephrol Dial Transplant. 2017;32(2):393\u20139.","journal-title":"Nephrol Dial Transplant"},{"issue":"5","key":"644_CR30","doi-asserted-by":"publisher","first-page":"e0196552","DOI":"10.1371\/journal.pone.0196552","volume":"13","author":"KA Sablik","year":"2018","unstructured":"Sablik KA, Clahsen-van Groningen MC, Hesselink DA, van Gelder T, Betjes MGH. Tacrolimus intra-patient variability is not associated with chronic active antibody mediated rejection. PLoS ONE. 2018;13(5):e0196552.","journal-title":"PLoS ONE"},{"issue":"7","key":"644_CR31","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1007\/s00228-019-02643-y","volume":"75","author":"R Rahamimov","year":"2019","unstructured":"Rahamimov R, Tifti-Orbach H, Zingerman B, Green H, Schneider S, Chagnac A, et al. Reduction of exposure to tacrolimus trough level variability is associated with better graft survival after kidney transplantation. Eur J Clin Pharmacol. 2019;75(7):951\u20138.","journal-title":"Eur J Clin Pharmacol"}],"container-title":["European Journal of Drug Metabolism and Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-020-00644-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13318-020-00644-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-020-00644-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T21:33:33Z","timestamp":1696628013000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13318-020-00644-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["644"],"URL":"https:\/\/doi.org\/10.1007\/s13318-020-00644-2","relation":{},"ISSN":["0378-7966","2107-0180"],"issn-type":[{"type":"print","value":"0378-7966"},{"type":"electronic","value":"2107-0180"}],"subject":[],"published":{"date-parts":[[2020,9,4]]},"assertion":[{"value":"4 September 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No funding was received to conduct this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare that they have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee (Ethics Committee of Faculty of Medicine, University of Nis (no. 12-2307-2\/5 from 10.03.2016. and no. 12-6972-2\/5 from 02.07.2018)) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The datasets generated during and\/or analysed during the current study are available from the corresponding author on reasonable request.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}}]}}