International Journal of Clinical Pharmacy

, Volume 41, Issue 1, pp 88–95 | Cite as

Effect of CYP3A5 genotype on hospitalization cost for kidney transplantation

  • Suda Vannaprasaht
  • Chulaporn LimwattananonEmail author
  • Sirirat Anutrakulchai
  • Chitranon Chan-on
Research Article


Background Dosage quantities of tacrolimus (TAC) vary according to cytochrome P450 3A5 (CYP3A5) genotype. Genotyping is expected to optimize the response to TAC response and to minimize adverse effects. In Thailand, kidney transplantation is reimbursable with the same diagnosis-related group payment regardless of patient’s CYP3A5 genotype. Objective This study aimed to determine the costs of TAC administration, therapeutic drug monitoring (TDM), and hospitalization for kidney transplantation across CYP3A5*1/*1, *1/*3, and *3/*3 genotypes. Setting A single transplant center in a university hospital. Method This is an observational study that collected data from patients pooled from both arms of a randomized controlled trial that tested initial doses of TAC. Main outcome measure TAC and TDM cost and hospitalization cost for transplantation were compared between genotypes. Results The CYP3A5*1/*1 patients had the highest median combined TAC–TDM cost and hospitalization cost ($1062 and $9097), followed by CYP3A5*1/*3 ($859 and $6467) and CYP3A5*3/*3 patients ($761 and $5604). The CYP3A5*1/*1 patients had a higher hospitalization cost by $2787 over the CYP3A5*1/*3 patients, despite marginal significance. The CYP3A5*1/*1 patients had a significantly higher cost of TAC plus TDM (by $309) and hospitalization cost (by $3275) than the CYP3A5*3/*3 patients. Both study costs were significantly higher in patients with delayed graft functioning than in patients with instant or slow graft functioning. Conclusion The benefits of genotype detection in patients with CYP3A5*1/*1 should be considered for a higher reimbursement rate because of the substantial differences in total hospitalization cost for kidney transplantation among patients with different CYP3A5 genotypes.


CYP3A5 Kidney transplantation Surgical cost Tacrolimus Thailand 



The authors thank Dr. Glenn Neville Borlace for providing editing assistance.


This study was funded by the National Science and Technology Development Agency (Project No. P-12-01486), the National Center for Genetic Engineering and Biotechnology, Thailand (BIOTEC), Chronic Kidney Disease Prevention in the Northeast of Thailand Project, and Faculty of Medicine, Khon Kaen University, Thailand.

Conflicts of interest

All authors declare that they have no conflicts of interest.


  1. 1.
    The Nephrology Society of Thailand. Cost of kidney transplantation in Thailand. Accessed 12 Dec 2017.
  2. 2.
    Yaowakulpatana K, Vadcharavivad S, Ingsathit A, Areepium N, Kantachuvesiri S, Phakdeekitcharoen B, et al. Impact of CYP3A5 polymorphism on trough concentrations and outcomes of tacrolimus minimization during the early period after kidney transplantation. Eur J Clin Pharmacol. 2016;72(3):277–83.CrossRefGoogle Scholar
  3. 3.
    Shuker N, Bouamar R, van Schaik RH, Clahsen-van Groningen MC, Damman J, Baan CC, et al. A randomized controlled trial comparing the efficacy of Cyp3a5 genotype-based with body-weight-based tacrolimus dosing after living donor kidney transplantation. Am J Transplant. 2016;16(7):2085–96.CrossRefGoogle Scholar
  4. 4.
    Thervet E, Loriot MA, Barbier S, Buchler M, Ficheux M, Choukroun G, et al. Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin Pharmacol Ther. 2010;87(6):721–6.Google Scholar
  5. 5.
    Kuypers DR, de Jonge H, Naesens M, Vanrenterghem Y. A prospective, open-label, observational clinical cohort study of the association between delayed renal allograft function, tacrolimus exposure, and CYP3A5 genotype in adult recipients. Clin Ther. 2010;32(12):2012–23.CrossRefGoogle Scholar
  6. 6.
    Maes BD, Kuypers D, Messiaen T, Evenepoel P, Mathieu C, Coosemans W, et al. Posttransplantation diabetes mellitus in FK-506-treated renal transplant recipients: analysis of incidence and risk factors. Transplantation. 2001;72(10):1655–61.CrossRefGoogle Scholar
  7. 7.
    Barry A, Levine M. A systematic review of the effect of CYP3A5 genotype on the apparent oral clearance of tacrolimus in renal transplant recipients. Ther Drug Monit. 2010;32(6):708–14.CrossRefGoogle Scholar
  8. 8.
    Vannaprasaht S, Reungjui S, Supanya D, Sirivongs D, Pongskul C, Avihingsanon Y, et al. Personalized tacrolimus doses determined by CYP3A5 genotype for induction and maintenance phases of kidney transplantation. Clin Ther. 2013;35(11):1762–9.CrossRefGoogle Scholar
  9. 9.
    Min SI, Kim SY, Ahn SH, Min SK, Kim SH, Kim YS, et al. CYP3A5*1 allele: impacts on early acute rejection and graft function in tacrolimus-based renal transplant recipients. Transplantation. 2010;90(12):1394–400.CrossRefGoogle Scholar
  10. 10.
    Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015;98(1):19–24.CrossRefGoogle Scholar
  11. 11.
    MacPhee IA, 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.CrossRefGoogle Scholar
  12. 12.
    Cho JH, Yoon YD, Park JY, Song EJ, Choi JY, Yoon SH, Park SH, et al. Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients. Transpl Proc. 2012;44(1):109–14.CrossRefGoogle Scholar
  13. 13.
    Glowacki F, Lionet A, Buob D, Labalette M, Allorge D, Provôt F, Hazzan M, et al. CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation. Nephrol Dial Transplant. 2011;26(9):3046–50.CrossRefGoogle Scholar
  14. 14.
    Gervasini G, Garcia M, Macias RM, Cubero JJ, Caravaca F, Benitez J. Impact of genetic polymorphisms on tacrolimus pharmacokinetics and the clinical outcome of renal transplantation. Transpl Int. 2012;25(4):471–80.CrossRefGoogle Scholar
  15. 15.
    Hu RH, Lee PH, Tsai MK. Clinical influencing factors for daily dose, trough level, and relative clearance of tacrolimus in renal transplant recipients. Transpl Proc. 2000;32(7):1689–92.CrossRefGoogle Scholar
  16. 16.
    Herrero MJ, Sánchez-Plumed J, Galiana M, Bea S, Marqués MR, Aliño SF. Influence of pharmacogenetic polymorphisms in routine immunosuppression therapy after renal transplantation. Transpl Proc. 2010;42(8):3134–6.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Suda Vannaprasaht
    • 1
  • Chulaporn Limwattananon
    • 2
    Email author
  • Sirirat Anutrakulchai
    • 3
  • Chitranon Chan-on
    • 3
  1. 1.Department of Pharmacology, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  2. 2.Division of Clinical Pharmacy, Faculty of Pharmaceutical SciencesKhon Kaen UniversityKhon KaenThailand
  3. 3.Department of Medicine, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand

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