ArticleTherapeutic drug monitoring2025
Effect of CYP3A4 Methylation on Tacrolimus Pharmacokinetics.
Article in Therapeutic drug monitoring, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCommon genetic variants in CYP3A4 together only explain a limited amount of the variability in tacrolimus clearance. This cross-sectional study aimed to explore the extent to which pharmacokinetic variability can be explained by methylation of the CYP3A4 gene.
methodsResidual tissue material from liver biopsies routinely collected 6 months post-transplantation was used. Inclusion criteria were tacrolimus once daily (Advagraf) in a steady state (ie, no dose change in the previous 3 days); assessment of tacrolimus pharmacokinetics within 3 weeks of the biopsy; and no documented episode of rejection for at least 3 months prior. Patients and liver donor tissue were genotyped. Only patients in which the patient and the donor had a genotype that did not express the CYP3A5 protein were included. The liver biopsy tissue material was then analyzed using an Illumina Infinium MethylationEPIC array.
resultsOf the 28 patients who met the inclusion criteria, 23 passed the quality control assessment required for the methylation analysis. Increased methylation of 1 of the 10 methylation probes within the CYP3A4 gene region (cg19046783) was positively correlated (Spearman correlation coefficient, 0.52) with the dose-normalized area under the concentration versus time curve (AUC) 0-24h ( P = 0.01). When quantified using univariate linear regression, this probe explained 18% of the variation in the dose-normalized AUC 0-24h . Interestingly, cg19046783 had the lowest mean methylation and highest biological variation.
conclusionsIncreased methylation of 1 of the 10 methylation probes within the CYP3A4 gene region (cg19046783) was positively correlated with increased dose-normalized AUC 0-24h , which explained 18% of the variation in the dose-normalized AUC 0-24h using univariate linear regression.
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