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Updated: Feb 26, 2026
08:38
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
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Association Between Tacrolimus Pharmacokinetics and Cytochrome P450 3A5 and Multidrug Resistance Protein 1 Exon 21
M Soda1, M Fujitani1, R Michiuchi1
1Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Transplantation Proceedings
|July 25, 2017
Summary
Genetic variations in CYP3A5 and MDR1 influence tacrolimus (TAC) pharmacokinetics in Japanese kidney transplant patients. Patients with combined CYP3A5*3/*3 and MDR1 G2677A genotypes require careful monitoring for optimal TAC dosing.
Area of Science:
- Pharmacogenomics
- Immunosuppression Therapy
- Transplantation Medicine
Background:
- Individual variability in tacrolimus (TAC) pharmacokinetics (PK) is linked to genetic polymorphisms in CYP3A5 and MDR1.
- Understanding these genetic influences is crucial for optimizing TAC therapy.
Purpose of the Study:
- To investigate the impact of single-nucleotide polymorphisms (SNPs) in CYP3A5 and MDR1 (exons 21 and 26) on TAC PK parameters in Japanese renal transplant recipients.
Main Methods:
- Genotyping for CYP3A5 and MDR1 (exons 21, 26) using PCR-RFLP in 38 Japanese renal transplant patients.
- TAC concentrations measured 3 weeks post-transplant, with PK parameters calculated.
Main Results:
- CYP3A5 expressers had significantly higher area under the curve (AUC) compared to non-expressers (CYP3A5*3/*3).
- MDR1 exon 21 G2677A allele carriers exhibited higher dose-adjusted AUC (AUC/D) and received lower TAC doses.
- Combined CYP3A5*3/*3 and MDR1 G2677A genotypes were associated with lower TAC doses and higher dose-adjusted trough levels (C/D) and AUC/D.
Conclusions:
- Patients with both CYP3A5*3/*3 and MDR1 G2677A genotypes show higher blood TAC concentrations.
- A significant portion (24%) of Japanese patients possess these combined mutations, necessitating careful monitoring and potential dose adjustments for TAC.
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