Evaluation of the Current Regimen of Tacrolimus in Patients with Hematopoietic Stem Cell Transplantation

조혈모세포 이식환자에서의 현행 tacrolimus 치료방법 평가

  • Yeo, Mi-Jin (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Park, Soo-Jin (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Bang, Joon-Seok (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • La, Hyen-Oh (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea)
  • 여미진 (가톨릭대학교 서울성모병원 약제부) ;
  • 박수진 (가톨릭대학교 서울성모병원 약제부) ;
  • 방준석 (가톨릭대학교 서울성모병원 약제부) ;
  • 나현오 (가톨릭대학교 서울성모병원 약제부)
  • Received : 2010.09.30
  • Accepted : 2010.11.20
  • Published : 2010.12.31

Abstract

Tacrolimus, an immunosuppressant prescribed against graft-versus-host disease (GVHD) in patients with allogeneichematopoietic stem cell transplantation (HSCT), is affected to change its pharmacokinetic properties by various factors. For this reason, it is needed a close monitoring to adjust dosage amount in order to optimize the blood concentration of tacrolimus is located within the effective range. According to our in-house study, 62% of HSCT-patients were needed dosage-adjustment and it is necessary to optimize the current immunosuppressive regimen in clinical settings. A retrospective study was designed to evaluate the dosing regimen (converting ratio of IV:PO=1:4) of tacrolimus in HSCT patients (n=62). After collecting data from patient's profile and medical record, pharmacokinetic parameters were calculate and compared between the estimated and the actual values in the selected subjects (n=58). It was found that the bioavailabilty (BA) of oral tacrolimus was 40.5% very much different from that is known as 25%. It implies that the current protocol has a potent risk causes dose-related toxicities to the patients. Furthermore, analyses among factors demonstrated that there was no statistical significance between BA of tacrolimus and the variable factors. In the clinical perspectives, the current converting ratio of tacrolimus in patients with HSCT to be re-considered and an appropriate and optimal alternative regimen should be adopted to prevent GVHD and to increase the quality of life of patients.

Keywords

References

  1. Hiraoka A. Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogenic bone marrow transplantation. Bone Marrow Transplant 2001; 28: 181-5. https://doi.org/10.1038/sj.bmt.1703097
  2. Ferarra JL. Advances in the clinical management of GVHD. Best Pract Res Clin Haematol 2008; 21: 677-82. https://doi.org/10.1016/j.beha.2008.07.003
  3. Fay JW, Wingard JR, Antin JH, et al., FK506 (Tacrolimus) monotherapy for prevention of Graft-Versus-Host Disease After Histocompatible Sibling Allogenic Bone Marrow Transplantation. Blood 1996; 87: 3514-9.
  4. Arai S, Vogelsang GB. Management of graft-versus-host disease. Blood Rev 2000; 14: 190-204. https://doi.org/10.1054/blre.2000.0137
  5. Simpson D. Drug therapy for acute graft-versus-host disease prophylaxis. J Hemato Ther Stem Cell Res 2000; 9: 317-25. https://doi.org/10.1089/15258160050079425
  6. Lesley S. Tacrolimus, A further update of its use in the management of organ transplantation. Drugs 2003; 63: 1247-97. https://doi.org/10.2165/00003495-200363120-00006
  7. Yanada M. Tacrolimus instead of cyclosporine used for prophylaxis against graft-versus-host disease improves outcome after hematopoietic stem cell transplantation from unrelated donors, but not from HLA-identical sibling donors: a nationwide survey conducted in Japan. Bone Marrow Transplant 2004; 34: 331-7. https://doi.org/10.1038/sj.bmt.1704596
  8. Park K. A randomized, open-label, two-period, crossover bioavailability study of two oral formulations of tacrolimus in healthy Korean adults. Clin Ther 2007; 29: 154-62. https://doi.org/10.1016/j.clinthera.2007.01.016
  9. Jusko WJ, Thomson AW, Fung J, et al., Consensus document: therapeutic drug monitoring of tacrolimus (FK-506). Ther Drug Monit 1995; 17: 606-14. https://doi.org/10.1097/00007691-199512000-00011
  10. Staatz CE, Willis C, Taylor PJ, et al., Population pharmacokinetics of tacrolimus in adult kidney transplant recipients. Clin pharmacol Ther 2002; 72: 660-9. https://doi.org/10.1067/mcp.2002.129304
  11. Scott LJ, McKeage K, Keam SJ, et al., Taclorimus: A further update of its use in the management organ transplantation. Drugs 2003; 63: 1247-97. https://doi.org/10.2165/00003495-200363120-00006
  12. Felipe CR, Silva HT, Machado PG, et al., The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics ad therapeutic drug monitoring. Clin Transplant 2002; 16: 262-72. https://doi.org/10.1034/j.1399-0012.2002.01103.x
  13. Bekersky I, Dressler D, Alak A, et al., Comparative tacrolimus pharmacokinetics: Normal versus midly hepatically impaired subjects. J Clin Pharmacol 2001; 41: 628-35. https://doi.org/10.1177/00912700122010519
  14. Gaston S. Maintenance immunosuppression in the renal transplant recipient. An overview. Am J Kidney Dis 2001; 38: S25-S35. https://doi.org/10.1053/ajkd.2001.28923
  15. Holt DW. Therapeutic drug monitoring of immunosuppressive drugs in kidney transplantation. Curr Opin Nephrol Hypertens 2003; 11: 657-63.
  16. Jusko WJ, Piekoszewski W, Klintmalm GB, et al., Pharmacokinetics and of tacrolimus in liver transplant patients. Clin pharmacol Ther 1995; 57: 281-90. https://doi.org/10.1016/0009-9236(95)90153-1
  17. Mekki Q, Lee C, Aweeka F, et al., pharmacokinetics of tacrolimus (FK506) in kidney transplant patients. Clin Pharmacol Ther 1993; 53: 238.
  18. Rowland M, Tozer T. Clinical pharmacokinetics: Concepts and applications. 3rd ed. Baltimore, Williams & Willkins, 1995; 290-309, 313-339.
  19. Boswell GW, Bekersky I, Fay J, et al., Tacrolimus pharmacokinetics in BMT patients. Bone Marrow Transplant 1998; 21: 23-8. https://doi.org/10.1038/sj.bmt.1701054
  20. Quan D, Winter ME. Immunosuppressants: Cyclosporine, tacrolimus, and sirolimus, In: Basic clinical pharmacokinetics. 4th ed. Baltimore, MD, Lippincortt Williams & Wilkins, 2004: 228-250.
  21. Cattanneo D, Perico N, RemuzzinG. From pharmacokinetics to pharmacogenomics: a new approach to tailor immunosuppressive. Am J Transplant 2004; 4: 299-310. https://doi.org/10.1111/j.1600-6143.2004.00312.x
  22. Yagil Y, Yagil C. Pharmacogenomic considerations for immunosuppressive therapy. Pharmacogenomics 2003; 4: 309-13. https://doi.org/10.1517/phgs.4.3.309.22690
  23. Weinshilboum R. Inheritance and drug response. New Eng J Med 2003; 348: 529-37. https://doi.org/10.1056/NEJMra020021
  24. Evans WE, McLeod HL. Pharmacogenomics-drug disposition, drug targets and side effects. New Eng J Med 2003; 348: 538-49. https://doi.org/10.1056/NEJMra020526
  25. MacPhee IA, Tacrolimus pharmacogenetics: polymorphisms associated with expression of cytochrome P4503A5 and p-glycoprotein correlate with dose requirement. Transplantation 2002; 74: 1486-9. https://doi.org/10.1097/00007890-200212150-00002