Precision Dosing of Tacrolimus in Liver Transplantation: Integrating Donor-Recipient CYP3A5 Pharmacogenomics…

Cohort studyCPT: pharmacometrics & systems pharmacology· Sep 2026

Precision Dosing of Tacrolimus in Liver Transplantation: Integrating Donor-Recipient CYP3A5 Pharmacogenomics and Drug Interactions.

Virunya Komenkul, Prawat Chantharit, Piyawat Komolmit … Thitima Wattanavijitkul

Molecular Genetic PathologyCohort studyTreatmentQ1IF 2.9

Fluconazole use linked to 33% lower tacrolimus clearance after liver transplant.

Precision Dosing of Tacrolimus in Liver Transplantation: Integrating Donor-Recipient CYP3A5 Pharmacogenomics and Drug Interactions.

Virunya Komenkul … Thitima Wattanavijitkul

CPT: pharmacometrics & systems pharmacology · Sep 2026

Background

Tacrolimus dosing in liver transplantation is complicated by a narrow therapeutic index and high CYP3A5 genetic variability.

Purpose

This study aimed to determine the optimal structural model and develop a precision dosing algorithm.

Methods

Using Phoenix NLME, we rigorously compared linear versus Michaelis-Menten elimination structures.

n = 114 patients

Results

Patients taking fluconazole had 33% lower tacrolimus clearance, needing lower doses.

1.5mg eve

Fluconazole-treated (l

3mg eve

Fluconazole-treated (h

2.5mg eve

Fluconazole-free (low

7mg eve

Fluconazole-free (high

More results

CYP3A5 genotypes were determined for both recipients and donors.

The combined CYP3A5 genotype exhibited a distinct stepwise reduction in apparent clearance from the homozygous expressor to the non-expressor group.

Hemoglobin displayed a significant inverse relationship with clearance.

More results

Simulations confirmed that fluconazole-treated patients require substantially lower doses (1.5-3.0 mg every 12 h) compared with fluconazole-free patients (2.5-7.0 mg every 12 h).

“

Conclusion

We provide a model-informed dosing algorithm that accounts for combined recipient/donor genetics and drug interactions, which may improve target attainment in liver transplant populations.

Precision Dosing of Tacrolimus in Liver Transplantation: Integrating Donor-Recipient CYP3A5 Pharmacogenomics and Drug Interactions.

Precision Dosing of Tacrolimus in Liver Transplantation: Integrating Donor-Recipient CYP3A5 Pharmacogenomics and Drug Interactions.

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