본문 바로가기
KERD
논문KCI 등재

조혈모세포 이식환자에서의 현행 tacrolimus 치료방법 평가

2

조회

0

다운로드

2

인용

0

참고문헌

키워드

주제분류약학

초록

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 calculated 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.

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 calculated 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.

참고문헌 (25)

  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, 28, pp.181~185 (2001)
  2. Ferarra JL, "Advances in the clinical management of GVHD", Best Pract Res Clin Haematol, 21, pp.677~682 (2008)
  3. Fay JW, "FK506 (Tacrolimus) monotherapy for prevention of Graft-Versus-Host Disease After Histocompatible Sibling Allogenic Bone Marrow Transplantation", Blood, 87, pp.3514~3519 (1996)
  4. Arai S, "Management of graft-versus-host disease", Blood Rev, 14, pp.190~204 (2000)
  5. Simpson D, "Drug therapy for acute graft-versus-host disease prophylaxis", J Hemato Ther Stem Cell Res, 9, pp.317~325 (2000)
  6. Lesley S, "Tacrolimus, A further update of its use in the management of organ transplantation", Drugs, 63, pp.1247~1297 (2003)
  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, 34, pp.331~337 (2004)
  8. Park K, "A randomized, open-label, two-period, crossover bioavailability study of two oral formulations of tacrolimus in healthy Korean adults", Clin Ther, 29, pp.154~162 (2007)
  9. Jusko WJ, "Consensus document: therapeutic drug monitoring of tacrolimus (FK-506)", Ther Drug Monit, 17, pp.606~614 (1995)
  10. Staatz CE, "Population pharmacokinetics of tacrolimus in adult kidney transplant recipients", Clin pharmacol Ther, 72, pp.660~669 (2002)
  11. Scott LJ, "Taclorimus: A further update of its use in the management organ transplantation", Drugs, 63, pp.1247~1297 (2003)
  12. Felipe CR, "The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics ad therapeutic drug monitoring", Clin Transplant, 16, pp.262~272 (2002)
  13. Bekersky I, "Comparative tacrolimus pharmacokinetics: Normal versus midly hepatically impaired subjects", J Clin Pharmacol, 41, pp.628~635 (2001)
  14. Gaston S, "Gaston S. Maintenance immunosuppression in the renal transplant recipient. An overview", Am J Kidney Dis, 38, pp.S25~S35 (2001)
  15. Holt DW, "Therapeutic drug monitoring of immunosuppressive drugs in kidney transplantation", Curr Opin Nephrol Hypertens, 11, pp.657~663 (2003)
  16. Jusko WJ, "Pharmacokinetics and of tacrolimus in liver transplant patients", Clin pharmacol Ther, 57, pp.281~290 (1995)
  17. Mekki Q, "pharmacokinetics of tacrolimus (FK506) in kidney transplant patients", Clin Pharmacol Ther, 53, pp.238~ (1993)
  18. Rowland M, "Clinical pharmacokinetics: Concepts and applications. 3rd ed", pp.290~309 (1995), Williams & Willkins
  19. Boswell GW, "Tacrolimus pharmacokinetics in BMT patients", Bone Marrow Transplant, 21, pp.23~8 (1998)
  20. Quan D, "Immunosuppressants: Cyclosporine, tacrolimus, and sirolimus, In: Basic clinical pharmacokinetics. 4th ed", pp.228~250 (2004), Lippincortt Williams & Wilkins
  21. Cattanneo D, "pharmacokinetics to pharmacogenomics: a new approach to tailor immunosuppressive", Am J Transplant, 4, pp.299~310 (2004)
  22. Yagil Y, "Pharmacogenomic considerations for immunosuppressive therapy", Pharmacogenomics, 4, pp.309~313 (2003)
  23. Weinshilboum R, "Inheritance and drug response", New Eng J Med, 348, pp.529~537 (2003)
  24. Evans WE, "Pharmacogenomics-drug disposition drug targets and side effects", New Eng J Med, 348, pp.538~549 (2003)
  25. MacPhee IA, "Tacrolimus pharmacogenetics: polymorphisms associated with expression of cytochrome P4503A5 and pglycoprotein correlate with dose requirement", Transplantation, 74, pp.1486~1489 (2002)

관련 논문AI추천

이 간행물의 다른 논문 (14건)