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他克莫司在心脏移植患者体内的临床药动学(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2002年第2期
页码:
139-141,144
栏目:
临床研究
出版日期:
2002-03-01

文章信息/Info

Title:
Clinical pharmacokinetics of Tacrolimus in heart transplantation recipients
作者:
文爱东1;  蔡振杰2;  李　彤2;  赵　磊1;  王晓武2;  杨　光2
第四军医大学西京医院: 1. 药剂科, 2. 心血管外科中心, 陕西 西安 710033
Author(s):
WEN Ai-dong1;  CAI Zhen-jie2;  LI Tong2;  ZHAO Lei1;  WANG Xiao-wu2;  YANG Guang 2
1.Department of Pharmacy, 2.Center of Cardiovascular Surgery, Xijing Hospital, Fourth military medical uiversity, Xi’an Shaanxi 710033, China
关键词:
他克莫司;  药代动力学;  心脏移植;  合理用药
Keywords:
Tacrolimus ;  pharmacokinetics;  heart transplantation;  rational drug-use
分类号:
R969.1
DOI:
-
文献标识码:
A
摘要:
目的 了解他克莫司在心脏移植患者体内的药代动力学特征 ,为患者实施用药的个体化。方法 采集 4例心脏移植患者稳态时一个用药间隔 (τ)内 9个不同时间点血样 ,以微粒子酶标免疫分析法 (MEIA)测定全血中他克莫司的浓度 ,计算他克莫司在个体患者体内的药动学参数 ,并以此参数为依据实施用药的个体化。以他克莫司谷浓度结合患者临床疗效及不良反应的情况 ,总结他克莫司在心脏移植术后的治疗窗。结果 患者口服他克莫司 (4～ 5mg/ 8h)后 ,其体内处置为一室开放模型 ,平均药动学参数 Tm ax,Cmax,T1 /2 ke和 AUC依次分别为 1.2± 0 .4h,2 9± 7m g· L- 1 ,7.6± 1.2 h和 2 75± 10 8mg· h- 1 · L- 1 。术后 1年来他克莫司谷浓度控制在 2 5～ 5 m g· L- 1 ,患者未出现严重的排斥或中毒反应。结论 他克莫司药动学的个体差异较大 ,应加强全血谷浓度监测 ,确保用药的安全有效。他克莫司在心脏移植的治疗窗 (谷浓度 )为 :0～ 1个月 15～ 2 0 mg· L- 1 ,1～ 3个月 10～ 15 mg· L- 1 ,3～ 6个月8～ 12 m g· L- 1 ,6个月后 5～ 8mg· L- 1 ,此浓度范围即可有满意的免疫抑制效果 ,又可减少他克莫司不良反应。
Abstract:
AIM To investigate the clinical pharmacokinetics of tacrolimus in heart transplantation recipients and to provide gist for clinical individual dosage. METHODS When level of tacrolimus was in a steady state, the whole blood samples of the 4 heart transplant recipients were collected for 9 times in scheduled time during a τ. The whole blood concentrations of tacrolimus were analyzed by microparticle enzyme immunoassay (MEIA) before and after the administration of the medicine, the concentration-time data was fitted with the computer software package PKBP-N1, and the parameters of pharmacokinetics were calculated. The patients were given individual medication of tacrolimus according to the parameters of pharmacokinetics. The treatment window of tacrolimus was concluded by clinical curative effect and adverse drug reaction (ADR) of the patients. RESULTS Compartmental analysis yielded a one-compartment open model in the steady state after oral administration of tacrolimus 4～5 mg/8 h. The mean pharmacokinetics parameters of tacrolimus were as follows: the Tmax = 1.2±0.4 h ,Cmax = 29±7 mg·L -1 , t 1/2 Ke = 7.6±1.2 h, AUC=275±108 mg·h -1 ·L -1 , respectively. The heart rejection and ADR of tacrolimus did not occur in 1 year after the operation when tacrolimus whole blood trough concentration was 25～5 mg·L -1 . CONCLUSION The pharmacokinetics of tacrolimus was highly variable among patients. The whole blood trough concentration of tacrolimus should be monitored to ensure safety and efficacy. The range of therapeutic window trough levels of tacrolimus was 15～20 mg·L -1 within the first month, 10～15 mg·L -1 within the second and third months,8～12 mg·L -1 within the fourth to sixth months,5～8 mg·L -1 from the seventh month after the transplantation. This range of therapeutic window of tacrolimus was ideal for heart transplant recipients with less rejection and ADR.

参考文献/References

[1] Jiang H, Kobayashi M. Differences between cyclosporine A and tacrolimus in organ transplantation [J]. Transplant Proc,1999, 31: 1978.

[2] Tanaka H, Kuroda A ,Marusawa H, et al. Physicochemical properties of FK506 , a novel immunosuppressant isolated from Streptomyces tsukubaensis [J]. Transplant proc, 1987, 19( suppl 6) : 11.

[3] 文爱东, 王为忠, 赵　磊, 等. 他克莫司在国内首例亲体小肠移植患者体内的药动学[J]. 中华器官移植杂志. 2001; 22 (3) :189.

[4] 孙国成, 蔡振杰, 刘维永, 等. 同种原位心脏移植外科围术期处理[J]. 第四军医大学学报, 2000, 21 (5) : 557.

[5] Asante KA ,Boyle GJ ,Webber SA , et al. Experience of FK506 immunesuppression in pediatric heart transplantation: a study of long - term adverse effects [J]. J Heart Lung Transplant.1996, 15 (4) : 415.

[6] Ko WJ , Chou NK, Chen YS, et al. Clinical trial of FK506 in heart transplant patients in Taiwan: report of 7 cases with immunosuppression switch from cyclo sporine to FK506 [J].Transplant Proc, 1998, 30 (7) : 3339.

[7] Undre NA , Meiser BM ,Uberfuhr P, et al. Pharmacok inetics of tacrolimus (FK506) in primary orthotopic heart transplant patients [J]. Transplant Proc, 1998, 30 (4) : 1112.

[8] Mentzer RM , Jahania MS, Lasley RD, et al. Tacrolimus as a rescue immunosuppressant after heart and lung transplantation [J]. Transplantation, 1998, 65 (1) : 109.

[9] Dressler BD, Colburn W , Mekki Q. Bioequivalence of 1 and 5 mg tacrolimus capsules using a replicate study design [J]. J Clin Pharmacol, 1999, 39: 1032.

[10] Herbert MF, Fisher RM , marsh Cl, et al. Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers [J]. J Clin Pharmacol, 1999, 39: 91.

[11] Mario BR, Mauro R, Mariadelfin A , et al. Clinical pharmacokinetics of tacrolimus in heart transplant recipients [J]. Ther Drug Monit, 1999, 21 (1) : 2.

[12] Sewing KF. Pharmacok inetics, Dosing principles, and blood level monitoring of FK506 [J]. Transplant proc, 1994, 26:3267- 3269.

备注/Memo

备注/Memo:
收稿日期：2001-06-18.
更新日期/Last Update: 2002-03-01