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, Sukhwinder Singh Sangha, DM Nephrology Dept of Nephrology , AIIMS New Delhi Search for other works by this author on: Oxford Academic Sushma Yadav, MS Obs & Gynecology Ex Senior resident, SHKM GMC, Nuh , Haryana, India Search for other works by this author on: Oxford Academic Raj Kanwar Yadav, DM Nephrology Dept of Nephrology , AIIMS New Delhi Corresponding author: Raj Kanwar Yadav, DM Nephrology, Additional Prof, Dept of Nephrology, AIIMS New Delhi, e mail: rkyadavnephrology@gmail.com, Ph 9013949622, Postal Dept of Nephrology, AIIMS New Delhi, India. Search for other works by this author on: Oxford Academic Asheesh Kumar, DM Nephrology Dept of Nephrology , AIIMS New Delhi Search for other works by this author on: Oxford Academic V Seenu, MS General surgery Dept of Nephrology , AIIMS New Delhi Dept of surgery , AIIMS New Delhi Search for other works by this author on: Oxford Academic S K Agarwal, DNB Nephrology, Ex Prof and head Dept of Nephrology , AIIMS New Delhi Dept of Paediatrics , Division of Genetics, AIIMS New Delhi Search for other works by this author on: Oxford Academic Madhulika Kabra, MD Paediatrics, Prof Dept of Nephrology , AIIMS New Delhi Dept of Paediatrics , Division of Genetics, AIIMS New Delhi Search for other works by this author on: Oxford Academic Madhumita Roy Chowdhury, PHD Senior scientist, Dept of Paediatrics , Division of Genetics, AIIMS New Delhi Search for other works by this author on: Oxford Academic Vishal Kumar Vishwakarma, MSc, Senior research fellow Dept of Nephrology , AIIMS New Delhi Search for other works by this author on: Oxford Academic D Bhowmik, DNB Nephrology, Prof and head Dept of Nephrology , AIIMS New Delhi Search for other works by this author on: Oxford Academic
RPS Pharmacy and Pharmacology Reports, rqae016, https://doi.org/10.1093/rpsppr/rqae016
Published:
06 June 2024
Article history
Received:
25 January 2024
Published:
06 June 2024
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Sukhwinder Singh Sangha, Sushma Yadav, Raj Kanwar Yadav, Asheesh Kumar, V Seenu, S K Agarwal, Madhulika Kabra, Madhumita Roy Chowdhury, Vishal Kumar Vishwakarma, MSc, Senior research fellow, D Bhowmik, Pattern of CYP3A5 and MDR-1 single nucleotide polymorphism and its impact on Tacrolimus levels and clinical outcomes in living renal allograft recipient, RPS Pharmacy and Pharmacology Reports, 2024;, rqae016, https://doi.org/10.1093/rpsppr/rqae016
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Abstract
Introduction
Renal transplant is best form of renal replacement therapy. Most favored immunosuppression includes Tacrolimus, mycophenolate mofetil and steroids. Tacrolimus has narrow therapeutic index and requires therapeutic drug monitoring (TDM). However, there is wide variation in tacrolimus level with weight based fixed dosage regimens. This variability is due to polymorphism of major pathways of metabolism ie CYP3A5 and MDR1 genes. Fast metabolizer require higher dosage and slow metabolizer require lower dosage. Genotype based dosing strategy may be useful to achieve early therapeutic level and reduce infections and rejections.
Methodology
160 transplant patients at tertiary care hospital in India were included in this study from 2016 to 2018. Genetic polymorphism analysis in CYP3A5 and MDR1 gene was carried out at time of transplant. All patients were given a fixed weight-based dosage of Tacrolimus. Data was analyzed in relation to genotype polymorphism.
Results and discussion
69.2% of Wild variants of CYP 3A5 (Fast metabolizers) have low initial tacrolimus levels. 51.5% of hom*o variants (Slow metabolizers) have high initial tac levels. However, all variants achieve optimum tacrolimus levels at same time (mean 12.4 days). There were higher number of infections among slow metabolizers.
Conclusion
A fixed dosing regimen with TDM result in high and low initial tacrolimus levels in slow and fast metabolizers respectively and more infections in slow metabolizers. However, graft rejections being fewer in number, were not different. A larger sample with genotype based dosing is required to test such a strategy.
Graphical Abstract
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Genetic polymorphism, Tacrolimus level, CYP3A5, MDR-1, Graft Rejections, Infections
Accepted manuscripts
Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.
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© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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