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Open AccessArticle

Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study

1
Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy
2
Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via C. Valeria, 98125 Messina, Italy
3
Department of Economics Section of Statistical and Mathematical Sciences, University of Messina, Via dei Verdi, 98122 Messina, Italy
4
Grande Ospedale Metropolitano: “Bianchi-Melacrino-Morelli”, Via Giuseppe Melacrino, 89124 Reggio Calabria, Italy
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2020, 10(2), 47; https://doi.org/10.3390/jpm10020047
Received: 28 April 2020 / Revised: 22 May 2020 / Accepted: 29 May 2020 / Published: 1 June 2020
Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in 75 transplanted patients and to investigate if tacrolimus blood levels correlate with presence of genetic polymorphisms, thus modifying tacrolimus pharmacokinetics. CYP3A5*1 (G6986A), CYP3A4*1B (A392G), CYP3A4*22, ABCB1 (C3435T; C1236T; G2677A/T), SLCO1B1 (T521C), polymorphisms were analyzed. Based on the effect of their genotypes, patients were stratified into 5 groups: (1) reduced tacrolimus metabolism (RM), (2) increased metabolism (IM), (3) transporters polymorphisms (TM), (4) metabolism and transporter polymorphisms (AM) and (5) no mutations (Wild Type, WT). The percentage of the samples out of therapeutic range was significantly higher in the IM group than in the WT group (p = 0.001), as well as compared to the TM group (p = 0.004). Only IM pattern (p = 0.015) resulted as an independent predictor of number of tacrolimus blood levels out of therapeutic range. RM pattern (p = 0.006) was inversely related to the administered dose. Therefore, genotyping could become a standard practice before tacrolimus prescription thus decreasing side effects, increasing efficacy and reducing the economic burden for the national health system. View Full-Text
Keywords: pharmacogenetics; polymorphism; tacrolimus; immunosuppressant; therapeutic drug monitoring pharmacogenetics; polymorphism; tacrolimus; immunosuppressant; therapeutic drug monitoring
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Pallio, G.; Irrera, N.; Bitto, A.; Mannino, F.; Minutoli, L.; Rottura, M.; Pallio, S.; Altavilla, D.; Alibrandi, A.; Marciano, M.C.; Righi, M.; Mannucci, C.; Arcoraci, V.; Squadrito, F. Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study. J. Pers. Med. 2020, 10, 47.

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