Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study
Articolo
Data di Pubblicazione:
2020
Abstract:
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.
Tipologia CRIS:
14.a.1 Articolo su rivista
Keywords:
pharmacogenetics; polymorphism; tacrolimus; immunosuppressant; therapeutic drug monitoring
Elenco autori:
Pallio, Giovanni; Irrera, Natasha; Bitto, Alessandra; Mannino, Federica; Minutoli, Letteria; Rottura, Michelangelo; Pallio, Socrate; Altavilla, Domenica; Alibrandi, Angela; Marciano, Maria Concetta; Righi, Maria; Mannucci, Carmen; Arcoraci, Vincenzo; Squadrito, Francesco
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