Journal
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
Volume 43, Issue 2, Pages 181-188Publisher
WILEY
DOI: 10.1111/jcpt.12624
Keywords
cross-reactivity; CYP3A5 polymorphism; immunoassay; tacrolimus; therapeutic drug monitoring
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What is known and objectiveThe anti-tacrolimus antibodies used in commercial immunoassay methods have cross-reactivity with tacrolimus metabolites. The aim of this study was to investigate differences in the effects of CYP3A5 polymorphism on tacrolimus concentrations obtained by four immunoassay methods in renal transplant patients. MethodsSamples (n=508) were evaluated using four immunoassays (chemiluminescence enzyme immunoassay [CLIA], affinity column-mediated immunoassay [ACMIA], electrochemiluminescence immunoassay [ECLIA] and latex agglutination turbidimetric immunoassay [LTIA]). ResultsBland-Altman plots showed average biases of -0.12 (1.96SD: -1.30-1.05)ng/mL for CLIA, -0.30 (-1.59-1.00)ng/mL for ECLIA, 0.42 (-1.21-2.05)ng/mL for ACMIA and 1.88 (-0.51-4.28)ng/mL for LTIA, when considering the mean of the three immunoassays (CLIA, ECLIA and ACMIA). In multiple regression analysis, the difference (CLIAmean) was affected by haematocrit levels. Differences in ECLIA were correlated with red blood cell counts. For LTIA, CYP3A5 genotype and haematocrit levels were identified as independent predictors for this bias. What is new and conclusionThe results obtained by CLIA, ECLIA and ACMIA were not affected by CYP3A5 polymorphism. However, in LTIA, CYP3A5*1/*3-derived data exhibited an inverse relationship in Bland-Altman analysis (slope: -0.0824). Higher cross-reactivity with 12-hydroxy tacrolimus at lower concentrations may occur in patients with the CYP3A5*1/*3 genotype. Because patients with the CYP3A5*1 allele identified using LTIA may show higher blood concentrations of tacrolimus at lower target concentrations, for example 3.0ng/mL, compared with other immunoassay methods, there is a need for sufficient consideration of the interpretation of values measured by LTIA.
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