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Transplantation Research
Published in: Transplantation Research 1/2016

Open Access 01-12-2016 | Clinical trial protocol

The role of CYP3A5 polymorphism and dose adjustments following conversion of twice-daily to once-daily tacrolimus in renal transplant recipients

Authors: Alina S. R Zaltzman, Lauren A. Glick, Jeffrey S. Zaltzman, Michelle Nash, Michael Huang, G. V. Ramesh Prasad

Published in: Transplantation Research | Issue 1/2016

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Abstract

Background

Tacrolimus is available as twice-daily Prograf® (Tac-BID) and the once-daily formulation, Advagraf® (Tac-OD). Although therapeutically equivalent, some transplant recipients require dose adjustments to achieve similar tacrolimus trough concentrations [Tac C0] after conversion between formulations. Tacrolimus is primarily metabolized by cytochrome P450 3A5 (CYP3A5). We sought to determine whether genetic polymorphisms in the CYP3A5 enzyme; CYP3A5 *1/*1 and CYP3A5 *1/*3 (expressers) compared to CYP3A5 *3/*3 (non-expressers) could account for discrepancies in dose requirements following conversion from Tac-BID to Tac-OD.

Methods

A cohort of 60 renal transplant recipients (RTR) from our larger conversion study of 496 patients underwent additional testing for CY3A5 genetic polymorphisms. Analysis included demographics, tac dosing and [Tac C0] pre- and post-conversion and dosing changes relative to CYP3A5 genotypes. CYP3A5 genetic polymorphisms were identified through analysis of genomic DNA.

Results

Conversion from tac bid to tac OD in this cohort required a mean (SD) dose increase from 3.1 (1.0) mg/day to 3.8 (1.3) mg/day (p = 0.007), to achieve similar [Tac C0]. The *1/*3 expresser group required a greater percentage dose adjustment (56.7 %) in converting from Tac-BID to Tac-OD as compared to the *3/*3 non-expresser group (26.6 %). Similar findings were observed with the both expresser groups combined (*1/*1 &*1/*3). The expressers were significantly more highly represented in the East Asian cohort.

Conclusions

The CYP3A5 expresser polymorphism necessitates an increase in dosing upon conversion from Tac-BID to Tac-OD, with the expresser genotypes contributing significantly to this finding. Given the variability in frequency of CYP3A5 genotypes in various ethnic groups, future studies should account for both isoenzyme polymorphism and ethnicity in optimizing dosing requirements.

Trial registration

Clinical trials.gov identifier: NCT01884480
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Metadata
Title
The role of CYP3A5 polymorphism and dose adjustments following conversion of twice-daily to once-daily tacrolimus in renal transplant recipients
Authors
Alina S. R Zaltzman
Lauren A. Glick
Jeffrey S. Zaltzman
Michelle Nash
Michael Huang
G. V. Ramesh Prasad
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Transplantation Research / Issue 1/2016
Electronic ISSN: 2047-1440
DOI
https://doi.org/10.1186/s13737-016-0031-6

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