ArticleFrontiers in pharmacology2026
Combined donor-recipient CYP3A functional allele count as an independent predictor of tacrolimus pharmacokinetics after liver transplantation.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Tacrolimus (TAC) exhibits high pharmacokinetic variability post-liver transplantation (LT). Traditional models overlook the metabolic chimerism between recipient (intestinal) and donor (hepatic) genotypes. We aimed to evaluate a combined donor-recipient CYP3A functional allele count predicting TAC exposure. Methods: This retrospective study analyzed 1,350 TAC trough measurements from 99 LT recipients. Results: The combined CYP3A functional allele count was the strongest genetic predictor of TAC exposure. Using the most prevalent group (4 alleles) as reference in multivariable LMMs, dose-normalized exposure significantly decreased by 43% and 48% in pairs with 5 and 6 functional alleles, respectively (p < 0.001). This gene-dose relationship remained stable across ICU, ward, and outpatient phases. The combined metric captured 4.2% of baseline variance (marginal Conclusion: The combined donor-recipient CYP3A functional allele count provides a biologically coherent, temporally stable metric of TAC metabolism. Outperforming single-genome models, it offers a stratification tool to guide early post-operative initial dose strategies.
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