조혈모세포이식 환자에서 I.V. Cyclosporine 용량 조절 현황 고찰
Cyclosporine I.V. Dose Adjustment in Patients with Hematopoietic Stem Cell Transplantation
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background and purpose : Cyclosporine A (CsA) is the most used immunosuppressive agent to prevent grafts versus host diseases (GVHD) after allo-HSCT (Hematopoietic Stem Cell Transplantations). However, the pharmacokinetic and pharmacodynamic profiles of CsA are known to show individual variability. Our study is designed to document the CsA blood level and status of dose adjustment, and drug interactions between CsA and antifungal agents including ketoconazole and itraconazole. Methods : A retrospective evaluation of the electronic medical records was conducted including adult patients who received allo-HSCT at Seoul National University Bundang Hospital from August 1, 2013 to August 31, 2015. Results : A total of 30 patients were included in the study. On average, the starting dose of CsA was 4.9 mg/kg/days, 87 % of the patients did not reach the therapeutic goal. In order to reach the target blood level, patients were required up to three dose adjustments and 4.2 days. The proportion of the patients whose blood level was out of the target level was 66.7 %. Initial blood level and T1/2 of CsA among patients who concurrently used antifungal agents were higher than the control group. Conclusion : Reevaluation of initial CsA IV dose and frequent therapeutic dose monitoring for concurrent use of CsA and antifungal agents are required for using the interdisciplinary team approach.
Abstract
Background and purpose : Cyclosporine A (CsA) is the most used immunosuppressive agent to prevent grafts versus host diseases (GVHD) after allo-HSCT (Hematopoietic Stem Cell Transplantations). However, the pharmacokinetic and pharmacodynamic profiles of CsA are known to show individual variability. Our study is designed to document the CsA blood level and status of dose adjustment, and drug interactions between CsA and antifungal agents including ketoconazole and itraconazole. Methods : A retrospective evaluation of the electronic medical records was conducted including adult patients who received allo-HSCT at Seoul National University Bundang Hospital from August 1, 2013 to August 31, 2015. Results : A total of 30 patients were included in the study. On average, the starting dose of CsA was 4.9 mg/kg/days, 87 % of the patients did not reach the therapeutic goal. In order to reach the target blood level, patients were required up to three dose adjustments and 4.2 days. The proportion of the patients whose blood level was out of the target level was 66.7 %. Initial blood level and T1/2 of CsA among patients who concurrently used antifungal agents were higher than the control group. Conclusion : Reevaluation of initial CsA IV dose and frequent therapeutic dose monitoring for concurrent use of CsA and antifungal agents are required for using the interdisciplinary team approach.
참고문헌 (23)
- Janelle BP, "Pharmacotherapy", pp.2455~2472 (2011), McGraw-Hill Companies
- Camil EV, "Therapeutic drug monitoring of cyclosporine in transplanted patients; Possibilities, controversy, causes for failure", Farmacia, 60(5), pp.595~601 (2012)
- 구현정, "조혈모세포이식에서 정맥투여 Cyclosporine의 경구 전환시 용량제시", 병원약사회지, 25(3), pp.1~5 (2008), 한국병원약사회
- Choi JS, "Assessment of converting from intravenous to oral administration of cyclosporine A in pediatric allogenic hematopoietic stem cell transplant recipients", Bone Marrow Transplantation, 38(1), pp.29~35 (2006)
- Chao NJ, "Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease", N Engl J Med, 329(17), pp.1225~1230 (1993)
- Link H, "Transplantation of allogeneic CD34+ blood cells", Blood, 87(11), pp.4903~4909 (1996)
- Kim MG, "Population pharmacokinetics of cyclosporine in hematopoietic stem cell transplant patients;Consideration of genetic polymorphisms", Annals of Pharmacotherapy, 49(6), pp.622~630 (2015)
- Andrew DJ, "Cyclosporin; revisions on monitoring guidelines and review of current analytical methods", Ann Clin Biochem, 39(Pt 5), pp.424~435 (2002)
- David JQ, "Basic clinical pharmacokinetics", pp.250~276 (2010), Lippincott Williams & Willkins
- Han K, "Population pharmacokinetics of cyclosporine in transplant recipients", The AAPS Journal, 15(4) (2013)
- Porta B, "Population pharmacokinetics of cyclosporine in kidney transplant patients", Transplant Proc, 31(6), pp.2246~2247 (1999)
- Parke J, "Factors affecting oral cyclosporine disposition after heart transplantation;Bootstrap validation of a population pharmacokinetic model", Eur J Clin Pharmacol, 56(6-7), pp.481~487 (2000)
- Wu KH, "Population pharmacokinetics of cyclosporine in clinical renal transplant patients", Drug Metab Dispos, 33(9), pp.1268~1275 (2005)
- Canafax DM, "The chronopharmaceutics of cyclosporine and its metabolites in recipients of pancreas allografts", Transplant Proc, 20(2), pp.471~477 (1998)
- Gumbleton M, "The possible relationship between hepatic drug metabolism and ketoconazole enhancement of cyclosporine nephrotoxicity", Trnasplantation, 40(4), pp.454~455 (1985)
- Hauben M, "Cyclosporine neurotoxicity", Pharmacotherapy, 16(4), pp.576~583 (1996)
- Lake KD, "Over the counter medications in cardiac transplant recipients; Guidelines for use", Ann Pharmacother, 26(12), pp.1566~1575 (1992)
- Lindholm A, "Influence of cyclosporine pharmacokinetics, trough concentrations, and AUC monitoring on outcome after kidney transplantation", Clin Pharmacol Ther, 54(2), pp.205~218 (1993)
- Grevel J, "Prediction of acute graft rejection in renal transplantation; The utility of cyclosporine blood concentration", Pharm Res, 8(2), pp.278~281 (1991)
- Kishi T, "Optimal initial dose of oral cyclosporine in relation to its toxicities for graft-versushost disease prophylaxis following reduced intensity stem cell transplantation in Japanese patients", Bone Marrow Transplantation, 35(11), pp.1079~1082 (2005)
- Campana C, "Clinically significant drug interactions with cyclosporine; An update", Clin Pharmacokinet, 30(2), pp.141~179 (1996)
- Doring M, "Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation", Eur J Clin Microbio Infec Dis, 33(4), pp.629~638 (2014)
- Inoue Y, "Drug interactions between micafungin at high doses and cyclosporine A in febrile neutropenia patients after allogeneic hematopoietic stem cell transplantation", Int J Clin Pharmacol Ther, 50(11), pp.831~837 (2012)