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      비만환자의 조혈모세포이식 후 체중 적용 기준에 따른 Tacrolimus 초기 농도 비교 = Comparison of the Initial Concentration of Tacrolimus according to Weight Application Criteria after Hematopoietic Stem Cell Transplantation in Obese Patients

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      https://www.riss.kr/link?id=A107495139

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      다국어 초록 (Multilingual Abstract)

      Background : Tacrolimus is an immunosuppressive agent and is largely used to prevent graft-versus-host disease in hematopoietic stem cell transplantation patients. Tacrolimus requires therapeutic drug monitoring because of its narrow therapeutic range...

      Background : Tacrolimus is an immunosuppressive agent and is largely used to prevent graft-versus-host disease in hematopoietic stem cell transplantation patients. Tacrolimus requires therapeutic drug monitoring because of its narrow therapeutic range. The number of cases where the dose of tacrolimus was reduced in obese patients because the blood concentration was higher than the initial effective therapeutic range (10–15 ng/mL)is increasing. Therefore, this study attempted to assess the adequacy of early tacrolimus dosages and establish more suitable weight-based dosing strategies for obese patients.
      Methods : This was a retrospective study, conducted on patients 20 years of age or older who received tacrolimus from the day before transplantation from January 2019 to June 2020 in Seoul St. Mary’s Hospital. The blood concentration of tacrolimus in the actual body weight (ABW) group was obtained from the actual blood collection, from which patient-specific pharmacokinetic parameters were obtained. The expected blood concentration of tacrolimus in the ideal body weight (IBW) group was then calculated. To evaluate the adequacy of the tacrolimus dosage, the average blood concentration and the number of patients within the effective therapeutic range were investigated. To evaluate the risk of developing side effects and the reduction in therapeutic effects, the number of patients above and below the effective therapeutic range and their average tacrolimus level were compared based on ABW and IBW, respectively.
      Results : The average blood concentration of 74 patients was 18±5.7 ng/mL in the ABW group and 14±4.5 ng/mL in the IBW group (p<0.001). The number of patients within the effective therapeutic range was 22 (29.7%) in the ABW group and 35 (47.3%) in the IBW group (p=0.043).
      The number and average tacrolimus level of the patients above the effective therapeutic range were 50 (67.6%) and 20.6±5.1 ng/mL, respectively, in the ABW group and 25 (33.8%) and 19.1±3.5 ng/mL, respectively, in the IBW group. The number and the average tacrolimus level of patients below the effective therapeutic range were 2 (2.7%) and 8.8±0.7 ng/mL, respectively, in the ABW group and 14 (18.9%) and 8.7±1.0 ng/mL, respectively, in the IBW group. There was no statistical difference in the average tacrolimus levels of the patients above and below the effective therapeutic range (p=0.190 and p=0.908, respectively).
      Conclusion : In obese patients, the administration of tacrolimus based on IBW is more preferred than ABW-based administration. However, additional pharmacokinetic model studies are needed.

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      참고문헌 (Reference)

      1 Liu Z, "Weightbased tacrolimus trough concentrations post liver transplant" 49 (49): 79-83, 2019

      2 Brunet M, "Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy : Second Consensus Report" 41 (41): 261-307, 2019

      3 World Health Organization, "The Asia-Pacific perspective: redefining obesity and its treatment" 2000

      4 정지혜, "Tacrolimus 주사에서 경구로 투여 경로 변경 시 용량 설정비율의 변경에 따른 효과 비교" 한국병원약사회 30 (30): 330-342, 2013

      5 Trifilio SM, "Tacrolimus use in adult allogeneic stem cell transplant recipients receiving voriconazole : preemptive dose modification and therapeutic drug monitoring" 45 (45): 1352-1358, 2010

      6 Gao Y, "Tacrolimus in adult hematopoietic stem cell transplantation" 15 (15): 803-811, 2019

      7 Yanik G, "Tacrolimus (FK506) and methotrexate as prophylaxis for acute graftversus-host disease in pediatric allogeneic stem cell transplantation" 26 (26): 161-167, 2000

      8 Watanabe N, "Relationship between tacrolimus blood concentrations and clinical outcome during the first 4 weeks after SCT in children" 45 (45): 1161-1166, 2010

      9 Wong R, "Prognostic factors for outcomes of patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndromes undergoing allogeneic progenitor cell transplantation" 11 (11): 108-114, 2005

      10 Przepiorka D, "Practical considerations in the use of tacrolimus for allogeneic marrow transplantation" 24 (24): 1053-1056, 1999

      1 Liu Z, "Weightbased tacrolimus trough concentrations post liver transplant" 49 (49): 79-83, 2019

      2 Brunet M, "Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy : Second Consensus Report" 41 (41): 261-307, 2019

      3 World Health Organization, "The Asia-Pacific perspective: redefining obesity and its treatment" 2000

      4 정지혜, "Tacrolimus 주사에서 경구로 투여 경로 변경 시 용량 설정비율의 변경에 따른 효과 비교" 한국병원약사회 30 (30): 330-342, 2013

      5 Trifilio SM, "Tacrolimus use in adult allogeneic stem cell transplant recipients receiving voriconazole : preemptive dose modification and therapeutic drug monitoring" 45 (45): 1352-1358, 2010

      6 Gao Y, "Tacrolimus in adult hematopoietic stem cell transplantation" 15 (15): 803-811, 2019

      7 Yanik G, "Tacrolimus (FK506) and methotrexate as prophylaxis for acute graftversus-host disease in pediatric allogeneic stem cell transplantation" 26 (26): 161-167, 2000

      8 Watanabe N, "Relationship between tacrolimus blood concentrations and clinical outcome during the first 4 weeks after SCT in children" 45 (45): 1161-1166, 2010

      9 Wong R, "Prognostic factors for outcomes of patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndromes undergoing allogeneic progenitor cell transplantation" 11 (11): 108-114, 2005

      10 Przepiorka D, "Practical considerations in the use of tacrolimus for allogeneic marrow transplantation" 24 (24): 1053-1056, 1999

      11 Bauters T, "Practical considerations in the use of intravenous tacrolimus in hematopoietic stem cell transplantation patients. Journal of oncology pharmacy practice" 21 (21): 478-480, 2015

      12 De Baerdemaeker LE, "Pharmacokinetics in obese patients" 4 (4): 152-155, 2004

      13 Andrews LM, "Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose" 3 (3): e129-, 2017

      14 Iwasaki K, "Metabolism of tacrolimus(FK506)and recent topics in clinical pharmacokinetics" 22 (22): 328-335, 2007

      15 Sawamoto K, "Mechanisms of lower maintenance dose of tacrolimus in obese patients" 29 (29): 341-347, 2014

      16 Hagen PA, "Low mean post-transplantation tacrolimus levels in weeks 2-3 correlate with acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation from related and unrelated donors" 54 (54): 155-158, 2019

      17 Rodrigo E, "High initial blood levels of tacrolimus in overweight renal transplant recipients" 37 (37): 1453-1454, 2005

      18 Devine BJ, "Gentamicin therapy" 8 : 650-655, 1974

      19 Liu J, "Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506complexes" 66 (66): 807-815, 1991

      20 Ferrara JL., "Advances in the clinical management of GVHD" 21 (21): 677-682, 2008

      21 Goker H, "Acute graft-vs-host disease : pathobiology and management" 29 (29): 259-277, 2001

      22 Jasiak-Panek NM, "A randomized, open-label pharmacokinetic trial of tacrolimus extended-release dosing in obese de novo kidney transplant recipients" 33 (33): e13640-, 2019

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