Genotype-based tacrolimus dosing guidelines: with or without CYP3A4*22?
(2017) Pharmacogenomics — Vol. 18, p. 1473-1480 (2017)
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- Abstract
- To test the relevance of revisiting the genotype classification based on CYP3A5*3 solely by incorporating CYP3A4*22 information. Discriminant analysis of principal component was performed to evaluate the relevance of either the CYP3A (CYP3A5 + CYP3A4 genotypes) or CYP3A5*3 classification variables. This analysis was based on a linear combination of noncompartmental pharmacokinetics parameters. Discriminant analysis of principal component gave better results with CYP3A compared with CYP3A5*3 clustering. The centroid means of the pharmacokinetics variables were significantly different with CYP3A genotype clustering (p = 0.04) but not with CYP3A5*3 solely (p = 0.06). Canonical plots reveal a better delimitation of clusters with CYP3A genotype compared with CYP3A5*3 and the reciever operating characteristic curves confirm this better discriminative power. We provide strong arguments of incorporating CYP3A4*22 genotype in practice to fine-tune the existing Clinical Phamacogenetics Implementation Consortium guidelines in the Caucasian population.
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Elens, L., & Haufroid, V. (2017). Genotype-based tacrolimus dosing guidelines: with or without CYP3A4*22? Pharmacogenomics, 18, 1473-1480. https://doi.org/10.2217/pgs-2017-0131 (Original work published 2017)