소아 신장이식 환자에서 연령 및 성별에 따른 타크롤리무스의 약동학적 차이에 관한 단일기관 연구
Effects of Age and Sex on the Pharmacokinetics of Tacrolimus during Pediatric Kidney Transplantation: A Single Center Study
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목적: 소아 신장 이식 환자에서 흔히 사용되는 면역 억제제 타크롤리무스는 성별, 연령별, 인종별로 다양한 약동학적 특성이 있음이 알려져 있다. 본 연구는 우리나라 소아신장 이식 환자가 가지는 타크롤리무스의 약동학적 특징을 파악하고 관련되는 인자를 알아보기 위해 시행되었다. 방법: 경북대병원 소아청소년과에서 신장 이식을 시행받고 초기 면역 억제치료로 타크롤리무스가 사용된 환자 9명을 대상으로, 사용된 약 용량과 혈중 최저 농도 등을 후향적으로 조사하였고 이들의 약동학적 특성을 성인 대조군과 비교하였다. 결과: 남아의 평균 약 용량은 여아에 비해 유의하게 높았으나 혈중 최저 농도는 두 군 간에 유의한 차이가 없었고 청소율 또한 남아에서 유의하게 높았다. 12세 이상의 평균 약 용량은 12세 미만에 비해 낮았고 혈중 최저 농도는 높은 경향을 보였으나 유의한 차이는 없었다. 성인은 12세 이상, 미만 모두의 경우 보다 유의하게 약 용량이 적었으나 혈중 최저 농도에서는 유의한 차이가 없었다. 또한, 청소율와 반감기에서도 모두 유의한 차이를 보였다. 결론: 소아 신장 이식에서 사용되는 타크롤리무스는 나이가 어릴수록, 남아의 경우에 좀 더 많은 용량을 투여해야 할 가능성이 있음을 확인할 수 있었다. 우리나라 소아 신장 이식 환자에서 타크롤리무스의 적절한 치료용량을 확인하기 위해서는 이상의 관련인자에 대한 추가적인 전향적인 연구가 필요하다고 사료 된다.
Abstract
Purpose: The pharmacokinetics of tacrolimus, one of the most widely used immunosuppressive drugs, are known to vary by sex, age, and ethnicity during pediatric transplantation. This study assessed the pharmacokinetic characteristics and associated factors of tacrolimus in Korean children receiving a kidney transplant. Methods: We retrospectively reviewed the pharmacokinetic data (therapeutic dose, trough level, clearance, and half-life) of 9 children who were given tacrolimus as one of their initial immunosuppressive drugs after kidney transplantation. In addition, we compared the findings to data from 10 adult kidney transplant recipients. Results: The mean age of our pediatric patients was 13.9 years, and the maleto- female ratio was 4:5. The mean dose of tacrolimus was 0.19±0.14 mg/kg/ day. The mean dose of tacrolimus for males was 0.23±0.12 mg/kg/day, which was significantly higher than the dose for females (0.16±0.14 mg/kg/day). The trough level was not significantly different between both groups. The clearance rate of tacrolimus for males was also significantly higher than females. Although the dosage of tacrolimus for patients over the age of 12 years was lower (0.18±0.13 vs. 0.21±0.16 mg/kg/day) and the trough level was higher (8.2±4.5 vs. 7.2±4.2 mg/ mL) than that for patients under the age of 12 years, there was no significant difference between them. However, there were significant differences between children and adults in dose, clearance, and half-life of tacrolimus. Conclusion: Out study suggests that the pharmacokinetics of tacrolimus tends to vary with sex and age. Therefore, large-scale prospective studies are required to verify the proper therapeutic dosage of tacrolimus in Korean children.
참고문헌 (27)
- 강희경, "신이식 후 면역반응의 이해 2부 이식면역검사와 면역억제제", Childhood Kidney Diseases, 12(2), pp.133~142 (2008), 대한소아신장학회
- Ratanatharathorn V, "Phase III study comparing methotrexate and tacrolimus (Prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation", Blood, 92, pp.2303~2314 (1998)
- Nash RA, "A phase III study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors", Blood, 96, pp.2062~2068 (2000)
- Shapiro R, "Pediatric renal transplantation under tacrolimus-based immunosuppression", Transplantation, 67, pp.299~303 (1999)
- Masuda S, "An up-date review on individualized dosage adjustment of calcineurin inhibitors in organ transplant patients", Pharmacol Ther, 112, pp.184~198 (2006)
- Kim JS, "Effect of age, ethnicity, and glucocorticoid use on tacrolimus pharmacokinetics in pediatric renal transplant patients", Pediatr Transplant, 9, pp.162~169 (2005)
- Bowman LJ, "The role of tacrolimus in renal transplantation", Expert Opin Pharmacother, 9, pp.635~643 (2008)
- Ellis D, "Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation", Pediatr Nephrol, 8, pp.193~200 (1994)
- Dunn TB, "Long-term outcomes of a prospective trial of steroid withdrawal after kidney transplantation", Surgery, 125, pp.155~159 (1999)
- Sarwal MM, "Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation", Transplantation, 76, pp.1331~1339 (2003)
- Gummert JF, "Newer immunosuppressive drugs : a review", J Am Soc Nephrol, 10, pp.1366~1380 (1999)
- Matas AJ, "OPTN", SRTR 2011 annual data report: kidney, 2013, pp.13(suppl 1), 11~46
- Scott LJ, "Tacrolimus: a further update of its use in the management of organ transplantation", Drugs, 63, pp.1247~1297 (2003)
- ZhaoW, "Developmental pharmacogenetics of immunosuppressants in pediatric organ transplantation", Ther Drug Monit, 32, pp.688~699 (2010)
- Halloran PF, "Molecular mechanisms of new immunosuppres-sants", Clin Transplant, 10, pp.118~123 (1996)
- Naesens M, "Maturation of dose-corrected tacrolimus predose trough levels in pediatric kidney allograft recipients", Transplantation, 85, pp.1139~1145 (2008)
- 김정수, "신장 이식에 사용되는 주요 면역억제제와 약물 동력학 검사", Korean Journal of Pediatrics, 48(5), pp.476~480 (2005), 대한소아과학회
- Delaloye JR, "Limited sampling strategies for monitoring Tacrolimus in pediatric liver transplant recipients", Ther Drug Monit, 33, pp.380~386 (2011)
- Zhao W, "Limited sampling strategy for estimating individual exposure of Tacrolimus in pediatric kidney transplant patients", Ther Drug Monit, 33, pp.681~687 (2011)
- ShishidoS, "Pharma-cokinetics of Tacrolimus in pediatric renal transplant recipients", Transplant Proc, 33, pp.1066~1068 (2001)
- Filler G, "Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants", Nephrol Dial Transplant, 12, pp.1668~1671 (1997)
- McDiarmid SV, "Differences in oral FK506 dose requirements between adults and pediatric liver transplant patients", Transplantation, 55, pp.1328~1332 (1993)
- Wallemacq PE, "Pharmacokinetics of tacrolimus (FK506) in paediatric liver transplant recipients", Eur J Metab Pharmacokinet, 23, pp.367~370 (1998)
- Cherala G, "Tacrolimus pharmacokinetics in Hispanic children after kidney transplantation", Transplant Proc, 43, pp.3708~3712 (2011)
- Felipe CR, "The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring", Clin Transplant, 16, pp.262~272 (2002)
- Mancinelli LM, "The pharmacokinetics and metabolic disposition of tacrolimus: A comparison across ethnic groups", Clin Pharmacol Ther, 69, pp.24~31 (2001)
- Przepiorka D, "Tacrolimus clearance is age-dependent within the pediatric population", Bone Marrow Transplant, 26, pp.601~605 (2000)