The Monitoring of Immunosuppressive Therapy with Tacrolimus in Patients with Kidney Transplant, Based on the Pharmacokinetic Criteria

Open access


Background: Therapeutic drug monitoring (TDM) in patients with Chronic Kidney Disease (CKD) with kidney transplant, represents a major post transplant concern due to the characteristics of this special category of patients, particularities which can generate changes of the pharmacokinetic profile of the administered medication.

Material and methods: The current study is a retrospective pharmacokinetic study, over a period of 50 months, including a group of 36 kidney transplanted patients with CKD. Tacrolimus blood concentration was determined by a validated high-performance liquid chromatography method (HPLC), at a 12 hour time interval from the last administration of the immunosuppressive medication and before the following dose (Residual concentration, Cmin(trough)).

Results: During the monitoring of therapy, based on the pharmacokinetic criteria, 252 measurements of blood concentration were determined, 58 of these being outside the therapeutic window.

Conclusions: The results obtained show that it is mandatory to continue to monitor closely medical therapy based on the pharmacokinetic criteria in view of improving drug administration. The other ways of monitoring therapy: the clinical and biochemical criteria should not be overlooked. In addition, the interindividual variability of patients should be considered, as well as drug interaction which can alter the pharmacokinetics of tacrolimus.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Venkataraman L Burakoff SJ Sen R. FK-506 inhibits antigen receptor-mediated induction of C-rel in B and T lymphoid cells. J Exp Med. 1995;181:1091-1099.

  • 2. Plosker GL Foster RH. Tacrolimus: a further update of its pharmacology and therapeutic use in the management of organ transplantation. Drugs. 2000;59:323-389.

  • 3. Kang JS Lee MH. Overview of therapeutic drug monitoring. The Korean Journal of Internal Medicine. 2009;24:1-10.

  • 4. Wong G Howard K Chapman JR Chadban S et al. Comparative survival and economic benefits of deceased donor kidney transplantation and dialysis in people with varying ages and co-morbidities. PLoS ONE 2012;7:1-9.

  • 5. Schiff J Cole E Cantarovich M. Therapeutic monitoring of calcineurin inhibitors for the nephrologist. Clin J Am Soc Nephrol. 2007;2:374-384.

  • 6. Wallemacq P Armstrong VW Brunet M et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the european consensus conference. Ther Drug Monit. 2009;31:139-152.

  • 7. Stevens LA Coresh J Greene T Levey AS. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med. 2006 354:2473-2483.

  • 8. Koo DDH Welsh KI McLaren AJ et al. Cadaver versus living donor kidneys: Impact of donor factors on antigen induction before transplant. Kidney International 1999;56:1551-1559.

  • 9. Gjertson DW Cecka JM. Living unrelated donor kidney transplantation. Kidney International 2000;58:491-499.

  • 10. Kanellis J. Justification for living donor kidney transplantation. Nephrology 2010;15:S72-S79.

  • 11. Zivcic-Cosic S Trobonjaca Z Racki S. Immunosuppressive treatment for kidney transplantation. Prilozi 2011;32:87-103.

  • 12. Naesens M Kuypers DRJ Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4:481–508.

  • 13. Michael F. Crutchlow Roy D. Bloom. Transplant-associated hyperglycemia: A new look at an old problem.Clin J Am Soc Nephrol 2007;2:343–355.

  • 14. Pirsch J Bekersky I Vincenti F et al. Coadministration of tacrolimus and mycophenolate mofetil in stable kidney transplant patients: pharmacokinetics and tolerability. J Clin Pharmacol 2000;40:527-532.

  • 15. Hasselink DA Ngyuen H Wabbijin M et al. Tacrolimus dose requirement in renal transplant recipients is significantly higher when use in combination with corticosteroids. Br J Clin Pharmacol 2003;56:327-330.

  • 16. Butani L Berg G Makker SP. Effect of felodipine on tacrolimus in a renal transplant recipient. Transplantation 2002;73:159.

  • 17. Boubenider S Vincent I Lambotte O et al. Interaction between theophylline and tacrolimus in a renal transplant pacient. Nephrol Dial Transplant 2000;15:1066-1068.

  • 18. Floren LC Bekersky I Benet LZ et al. Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. Clin Farmacol Ther 1997;62:41-49.

  • 19. Michelangelo V Piero D Elisa C et al. Grapefruit juice and kinetics of tacrolimus. J Am Soc Nephrol 2001;12:862.

  • 20. Egashira K Fukuda E Onga T et al. Pomelo-induced increase in the blood level of tacrolimus in a renal transplant pacient. Transplantation 2003;75:1057.

  • 21. Kurzawski M Dąbrowska J Dziewanowski K et al. CYP3A5 and CYP3A4 but not ABCB1 polymorphisms affect tacrolimus dose-adjusted trough concentrations in kidney transplant recipients. Pharmacogenomics 2014;15:179-188.

Journal information
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 221 118 2
PDF Downloads 73 53 2