Therapeutic drug monitoring of tacrolimus in kidney transplant patients: Insights from an Indian tertiary care clinical setting

Chaitra Rao Karkal; Daksha Dineshchandra Shetty; Sara Hajizadeh Amzajerdi; Tejashree Pasumarthi; Shankar Prasad Nagaraju; Ravindra Attur Prabhu; Surulivelrajan Mallayasamy

doi:10.7324/JAPS.2025.211306

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Abstract

Kidney transplantation is the most recommended treatment for patients with end-stage kidney disease. The major problem faced with transplantation is allograft rejection, which can be prevented by administering immunosuppressants like tacrolimus. Tacrolimus level exhibits wide variability among individuals, making therapeutic drug monitoring important. This study aimed to understand the dosing protocol of tacrolimus in kidney transplant patients and to assess the relationship between dosage and concentration levels, in the absence of information on CYP3A5 genetic polymorphism. It was a retrospective observational study including 90 patients from a tertiary care teaching hospital, who were classified into two categories, followed from the transplantation and nFFT. Data were collected from in-patient files as well as electronic medical records. This study found that tacrolimus levels were proportionately increasing from 4 to 15 ng/ml with doses. Average initial doses were high (4.34 ± 1.73 mg) and tapered to (3 ± 0.46 mg) over the visits. There were deviations observed from anticipated levels in a certain number of patients, indicating a need for genotype testing before tacrolimus dosing to accurately determine initial doses. Including genetic data would be an appropriate measure for accurate dosage adjustment, especially during the initial stages post kidney transplant.

Keyword: Tacrolimus kidney transplantation tacrolimus trough concentrations inter-patient variability

Citation:

Karkal CR, Shetty DD, Amzajerdi SH, Pasumarthi T, Nagaraju SP, Prabhu RA, Mallayasamy S. Therapeutic drug monitoring of tacrolimus in kidney transplant patients: Insights from an Indian tertiary care clinical setting. J Appl Pharm Sci. 2025. Online First. http://doi.org/10.7324/JAPS.2025.211306

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

1. Statista [Internet]. Number of kidney transplants worldwide by region 2022. [cited 2024 Jul 6]. Available from: https://www.statista.com/statistics/398657/kidney-transplants-by-world-region/
2. Shroff S. Current trends in kidney transplantation in India. Indian J Urol. 2016;32(3):173. https://doi.org/10.4103/0970-1591.185092
3. Greanya ED, Poulin E, Partovi N, Shapiro RJ, Al-Khatib M, Ensom MHH. Pharmacokinetics of tacrolimus and mycophenolate mofetil in renal transplant recipients on a corticosteroid-free regimen. Am J Health Syst Pharm. 2012;69(2):134-42. https://doi.org/10.2146/ajhp110287
4. Yu M, Liu M, Zhang W, Ming Y. Pharmacokinetics, pharmacodynamics and pharmacogenetics of tacrolimus in kidney transplantation. Curr Drug Metab. 2018;19(6):513-22. https://doi.org/10.2174/1389200219666180129151948
5. Chen L, Prasad GVR. CYP3A5 polymorphisms in renal transplant recipients: influence on tacrolimus treatment. Pharmacogenomics Pers Med. 2018; 11:23-33. https://doi.org/10.2147/PGPM.S107710
6. Li L, Li CJ. Tacrolimus in preventing transplant rejection in Chinese patients -optimizing use. Drug Des Devel Ther. 2015;9:473-85. https://doi.org/10.2147/DDDT.S41349
7. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet. 2004;43(10):623-53. https://doi.org/10.2165/00003088-200443100-00001
8. Campagne O, Mager DE, Brazeau D, Venuto RC, Tornatore KM. Tacrolimus population pharmacokinetics and multiple CYP3A5 genotypes in black and white renal transplant recipients. J Clin Pharmacol. 2018;58(9):1184-95. https://doi.org/10.1002/jcph.1118
9. Liu XL, Guan YP, Wang Y, Huang K, Jiang FL, Wang J, et al. Population pharmacokinetics and initial dosage optimization of tacrolimus in pediatric hematopoietic stem cell transplant patients. Front Pharmacol. 2022;13:891648. https://doi.org/10.3389/fphar.2022.891648
10. Bansal S. Therapeutic drug monitoring of tacrolimus in kidney transplantation. Indian J Transplant. 2020;14(1):8. https://doi.org/10.4103/ijot.ijot_4_20
11. Kocur A, Marsza?ek D, Rubik J, Czajkowska A, Pawi?ski T. Therapeutic drug monitoring of tacrolimus based on volumetric absorptive microsampling technique (VAMS) in renal transplant pediatric recipients-LC-MS/MS method development, hematocrit effect evaluation, and clinical application. Pharmaceutics. 2023;15(1):299. https://doi.org/10.3390/pharmaceutics15010299
12. Nguyen TD, Smith NM, Attwood K, Gundroo A, Chang S, Yonis M, et al. Bayesian optimization of tacrolimus exposure in stable kidney transplant patients. Pharmacother J Hum Pharmacol Drug Ther. 2023;43(10):1032-42. https://doi.org/10.1002/phar.2848
13. Wallemacq P, Armstrong VW, Brunet M, Haufroid V, Holt DW, Johnston A, et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit. 2009;31(2):139-52. https://doi.org/10.1097/FTD.0b013e318198d092
14. Hwang YH, Kim H, Min K, Yang J. Tacrolimus trough levels in kidney transplant recipients. BMC Nephrol. 2021;22(1):405. https://doi.org/10.1186/s12882-021-02622-5
15. Lu Z, Bonate P, Keirns J. Population pharmacokinetics of immediate- and prolonged-release tacrolimus formulations in liver, kidney and heart transplant recipients. Br J Clin Pharmacol. 2019;85(8):1692-703. https://doi.org/10.1111/bcp.13952
16. Schagen MR, Volarevic H, Francke MI, Sassen SDT, Reinders MEJ, Hesselink DA, et al. Individualized dosing algorithms for tacrolimus in kidney transplant recipients: current status and unmet needs. Expert Opin Drug Metab Toxicol. 2023;19(7):429-45. https://doi.org/10.1080/17425255.2023.2250251
17. MacPhee IAM, Fredericks S, Tai T, Syrris P, Carter ND, Johnston A, et al. The influence of pharmacogenetics on the time to achieve target tacrolimus concentrations after kidney transplantation. Am J Transplant. 2004;4(6):914-9. https://doi.org/10.1111/j.1600-6143.2004.00435.x
18. Niioka T, Kagaya H, Saito M, Inoue T, Numakura K, Habuchi T, et al. Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation. Int J Mol Sci. 2015;16(1):1840-54. https://doi.org/10.3390/ijms16011840
19. Kantasiripitak W, Van Daele R, Gijsen M, Ferrante M, Spriet I, Dreesen E. Software tools for model-informed precision dosing: how well do they satisfy the needs? Front Pharmacol. 2020;11:620. https://doi.org/10.3389/fphar.2020.00620
20. Andrews LM, Hesselink DA, Van Schaik RHN, Van Gelder T, De Fijter JW, Lloberas N, et al. A population pharmacokinetic model to predict the individual starting dose of tacrolimus in adult renal transplant recipients. Br J Clin Pharmacol. 2019;85(3):601-15. https://doi.org/10.1111/bcp.13838

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Karkal C R [PubMed] [Google Scholar ]

Shetty D D [PubMed] [Google Scholar ]

Amzajerdi S H [PubMed] [Google Scholar ]

Pasumarthi T [PubMed] [Google Scholar ]

Nagaraju S P [PubMed] [Google Scholar ]

Prabhu R A [PubMed] [Google Scholar ]

S M [PubMed] [Google Scholar ]

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1. Statista [Internet]. Number of kidney transplants worldwide by region 2022. [cited 2024 Jul 6]. Available from: https://www.statista.com/statistics/398657/kidney-transplants-by-world-region/

2. Shroff S. Current trends in kidney transplantation in India. Indian J Urol. 2016;32(3):173. https://doi.org/10.4103/0970-1591.185092

3. Greanya ED, Poulin E, Partovi N, Shapiro RJ, Al-Khatib M, Ensom MHH. Pharmacokinetics of tacrolimus and mycophenolate mofetil in renal transplant recipients on a corticosteroid-free regimen. Am J Health Syst Pharm. 2012;69(2):134-42. https://doi.org/10.2146/ajhp110287

4. Yu M, Liu M, Zhang W, Ming Y. Pharmacokinetics, pharmacodynamics and pharmacogenetics of tacrolimus in kidney transplantation. Curr Drug Metab. 2018;19(6):513-22. https://doi.org/10.2174/1389200219666180129151948

5. Chen L, Prasad GVR. CYP3A5 polymorphisms in renal transplant recipients: influence on tacrolimus treatment. Pharmacogenomics Pers Med. 2018; 11:23-33. https://doi.org/10.2147/PGPM.S107710

6. Li L, Li CJ. Tacrolimus in preventing transplant rejection in Chinese patients -optimizing use. Drug Des Devel Ther. 2015;9:473-85. https://doi.org/10.2147/DDDT.S41349

7. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet. 2004;43(10):623-53. https://doi.org/10.2165/00003088-200443100-00001

8. Campagne O, Mager DE, Brazeau D, Venuto RC, Tornatore KM. Tacrolimus population pharmacokinetics and multiple CYP3A5 genotypes in black and white renal transplant recipients. J Clin Pharmacol. 2018;58(9):1184-95. https://doi.org/10.1002/jcph.1118

9. Liu XL, Guan YP, Wang Y, Huang K, Jiang FL, Wang J, et al. Population pharmacokinetics and initial dosage optimization of tacrolimus in pediatric hematopoietic stem cell transplant patients. Front Pharmacol. 2022;13:891648. https://doi.org/10.3389/fphar.2022.891648

10. Bansal S. Therapeutic drug monitoring of tacrolimus in kidney transplantation. Indian J Transplant. 2020;14(1):8. https://doi.org/10.4103/ijot.ijot_4_20

11. Kocur A, Marsza?ek D, Rubik J, Czajkowska A, Pawi?ski T. Therapeutic drug monitoring of tacrolimus based on volumetric absorptive microsampling technique (VAMS) in renal transplant pediatric recipients-LC-MS/MS method development, hematocrit effect evaluation, and clinical application. Pharmaceutics. 2023;15(1):299. https://doi.org/10.3390/pharmaceutics15010299

12. Nguyen TD, Smith NM, Attwood K, Gundroo A, Chang S, Yonis M, et al. Bayesian optimization of tacrolimus exposure in stable kidney transplant patients. Pharmacother J Hum Pharmacol Drug Ther. 2023;43(10):1032-42. https://doi.org/10.1002/phar.2848

13. Wallemacq P, Armstrong VW, Brunet M, Haufroid V, Holt DW, Johnston A, et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit. 2009;31(2):139-52. https://doi.org/10.1097/FTD.0b013e318198d092

14. Hwang YH, Kim H, Min K, Yang J. Tacrolimus trough levels in kidney transplant recipients. BMC Nephrol. 2021;22(1):405. https://doi.org/10.1186/s12882-021-02622-5

15. Lu Z, Bonate P, Keirns J. Population pharmacokinetics of immediate- and prolonged-release tacrolimus formulations in liver, kidney and heart transplant recipients. Br J Clin Pharmacol. 2019;85(8):1692-703. https://doi.org/10.1111/bcp.13952

16. Schagen MR, Volarevic H, Francke MI, Sassen SDT, Reinders MEJ, Hesselink DA, et al. Individualized dosing algorithms for tacrolimus in kidney transplant recipients: current status and unmet needs. Expert Opin Drug Metab Toxicol. 2023;19(7):429-45. https://doi.org/10.1080/17425255.2023.2250251

17. MacPhee IAM, Fredericks S, Tai T, Syrris P, Carter ND, Johnston A, et al. The influence of pharmacogenetics on the time to achieve target tacrolimus concentrations after kidney transplantation. Am J Transplant. 2004;4(6):914-9. https://doi.org/10.1111/j.1600-6143.2004.00435.x

18. Niioka T, Kagaya H, Saito M, Inoue T, Numakura K, Habuchi T, et al. Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation. Int J Mol Sci. 2015;16(1):1840-54. https://doi.org/10.3390/ijms16011840

19. Kantasiripitak W, Van Daele R, Gijsen M, Ferrante M, Spriet I, Dreesen E. Software tools for model-informed precision dosing: how well do they satisfy the needs? Front Pharmacol. 2020;11:620. https://doi.org/10.3389/fphar.2020.00620

20. Andrews LM, Hesselink DA, Van Schaik RHN, Van Gelder T, De Fijter JW, Lloberas N, et al. A population pharmacokinetic model to predict the individual starting dose of tacrolimus in adult renal transplant recipients. Br J Clin Pharmacol. 2019;85(3):601-15. https://doi.org/10.1111/bcp.13838