Examin Ethnicity and Pharmacogenetics of the Cohort Requiring Dose Adjustment Post-conversion Clinical Trial
Official title:
A Retrospective Analysis of Renal Function, Tac Dose Adjustments and CYP3A5 Pharmacogenetics in Stable Renal Transplant Recipients Converted From Tac BID to Tac OD
In Kidney transplant recipients Once daily Tacrolimus has the poteb]ntial advantage of
better adnerence, and perhpas improvement in reanl function compred with the twice daily
tacrolimus formulation.
Our center has the largest experience in North America with once-daily tacrolimus (
advagraf) in Renal transplant recipients.
Recently we converted ~500 stable patients from the twice daily to once-daily tacrolimus.
We are interested in:
1. change in renal function
2. dose changes based on ethnic diveristy
3. dose changes based on pharmacogenetics
This will helpnus understand better ways to utilize this anti-rejection medication
The Renal transplant program at St. Michael's is one of the largest in Canada. The CNI of
choice since 2000 has been tacrolimus based therapy. In 2009 our program decided to switch
from bid prograf to once daily advagraf for all de-novo renal transplant recipients (RTR).
Our Advagraf experience is currently the largest in North America. Because of concerns
regarding generic prograf, we began a conversion of > 600 prevalent transplant patients on
bid prograf to OD advagraf in January 2012. At present this is nearly completed.
It has been recognized that dosing of tacrolimus is highly dependent on pharmacogenentic
differences related to the CYP3A5 genotype. CYP3A%*3 (nonexpressors) require significantly
higher doses of tacrolimus than CYP3A5*1 (expressers) with heterozygotes being somewhere in
the middle. Our study will examine the demographics, renal function and tacrolimus dosing
and Co levels, both pre and post conversion from tac BID, to tac OD in our cohort of
converted patients.
Of More scientific interest, will be to retrospectively determine the CYP3A5 genotypes in
recipients who required significant dose adjustments in the tac OD following conversion and
compare to a matched cohort of recipients in whom no dose adjustment was needed.
The hypothesis is that recipients who require dose increase when converted from the BID to
the OD formulation, will have a different CYP3A5 genotype and will tend towards CYP3A5*3.
This will be the largest cohort to look at this question. Specifically this may lead to
better dosing of tac OD, if pre-emptive genotyping prior to transplantation were to be
employed.
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Observational Model: Cohort, Time Perspective: Retrospective