Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

01 December 2007

The CYP3A5*1/*3 single nucleotide polymorphism (SNP) determines the extent of drug interaction between tacrolimus and fluconazole in renal transplant recipients

H. de Jonge, M. Naesens, Y. Vanrenterghem, D. R. Kuypers

Ann Transplant 2008; 13(1): 34-35 :: ID: 880191


Background: Drug interactions between calcineurin-inhibitors and azole antifungals are characterized by a large clinical variability. The aim of this study was to examine the effect of CYP3A4, CYP3A5 and MDR1 SNPs on changes in tacrolimus trough concentrations and daily dose in renal transplant recipients treated with fluconazole.
Material/Methods: Out of 753 renal transplant recipients treated with tacrolimus, 29 patients were identified who received fluconazole treatment. These patients were genotyped for CYP3A4*1/*1B, CYP3A5*1/*3, MDR1 C3435T and G2677T/A and the effect of these SNPs on tacrolimus trough concentrations and dosing during fluconazole treatment was examined.
Results: Dose-corrected tacrolimus C0 did not increase significantly from baseline (1.26±1.23-fold) in heterozygous CYP3A5*1 carriers (n=6) during fluconazole therapy, as opposed to CYP3A5*3 homozygous patients (n=23) (3.28±2.34-fold; p=0.04 between CYP3A5*3/*3 and CYP3A5*3/*1 genotypes ). CYP3A5*3 homozygotes demonstrated a significant decrease in body weight-corrected tacrolimus dose during fluconazole administration (-54.7±23.7% from baseline, p<0.05) as opposed to heterozygous carriers of CYP3A5*1 (-25.1±29.9%; p=0.07 between CYP3A5*3/*3 and CYP3A5*3/*1 genotypes). These findings were not influenced by fluconazole dose or duration of treatment. More CYP3A5*3 homozygous patients were exposed to tacrolimus C0 ≥15 ng/mL during fluconazole therapy compared to CYP3A5*1 carriers (73.9% vs. 16.7%, p=0.01).
Conclusions: Renal transplant recipients with the CYP3A5*3/*3 genotype (non-expressers), are more susceptible for fluconazole-induced inhibition of tacrolimus metabolism as opposed to CYP3A5*1 carriers (expressers). Identification of this genetic determinant affecting the extent of this CYP3A-mediated drug interaction could potentially help to better manage drug interactions between tacrolimus and fluconazole.

Keywords: Tacrolimus, transplant, Broca


Most Viewed Current Articles

26 Jan 2022 : Review article  

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

DOI :10.12659/AOT.934924

Ann Transplant 2022; 27:e934924

24 Aug 2021 : Review article  

Normothermic Machine Perfusion (NMP) of the Liver – Current Status and Future Perspectives

DOI :10.12659/AOT.931664

Ann Transplant 2021; 26:e931664

29 Dec 2021 : Original article  

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...

DOI :10.12659/AOT.933588

Ann Transplant 2021; 26:e933588

15 Mar 2022 : Case report  

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...

DOI :10.12659/AOT.935860

Ann Transplant 2022; 27:e935860

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358