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肝移植中每日一次使用他克莫司:是“仿制药”,还是具有治疗优势?

Once-daily tacrolimus in liver transplantation: a 'me-too drug', or a therapeutic advantage.

作者信息

Trunečka Pavel

机构信息

Transplant Center, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.

出版信息

Curr Opin Organ Transplant. 2017 Apr;22(2):118-122. doi: 10.1097/MOT.0000000000000387.

Abstract

PURPOSE OF REVIEW

To provide latest information on differences between standard tacrolimus (TAC BID) and slow-released formulation of tacrolimus (Advagraf) in liver transplantation (LTx), and to discuss the latter's therapeutic value as a distinct entity.

RECENT FINDINGS

Two articles on de-novo studies, several on conversion and one on survival analysis from the European Liver Transplant Registry published recently showed that low-dose Advagraf immediately after transplantation provided same protection to the kidney as standard dose delayed until day 5, and was associated with lower rejection rate; to maintain the same trough level after late conversion to Advagraf, an approximately 1.25-fold higher dose was needed on average; if studied by questionnaire, conversion improved medication adherence; and registry data provided evidence of long-term survival benefit of Advagraf over TAC BID (7 and 8% graft and patient survival rates over a 3-year period; P < 0.002 and P < 0.003, respectively).

SUMMARY

Pharmacokinetic differences between TAC BID and Advagraf translate into less interpatient and intrapatient variability and improve adherence. If survival benefit of Advagraf administration de novo after LTx as demonstrated by the European Liver Transplant Registry analysis is confirmed in an independent cohort, Advagraf will leave the area of the 'me-too' drugs to become the immunosuppressant of choice.

摘要

综述目的

提供肝移植(LTx)中标准他克莫司(TAC BID)与他克莫司缓释制剂(Advagraf)之间差异的最新信息,并讨论后者作为一种独特药物的治疗价值。

最新发现

欧洲肝脏移植登记处最近发表的两篇关于从头研究的文章、几篇关于转换的文章以及一篇关于生存分析的文章表明,移植后立即使用低剂量Advagraf对肾脏的保护作用与延迟至第5天使用标准剂量相同,且排斥率较低;晚期转换为Advagraf后若要维持相同的谷浓度,平均需要约1.25倍高的剂量;通过问卷调查研究发现,转换可提高药物依从性;登记处数据提供了证据,表明Advagraf在长期生存方面优于TAC BID(3年期间移植物和患者生存率分别为7%和8%;P<0.002和P<0.003)。

总结

TAC BID与Advagraf之间的药代动力学差异导致患者间和患者内变异性降低,并提高了依从性。如果欧洲肝脏移植登记处分析所证明的LTx后从头给予Advagraf的生存益处能在一个独立队列中得到证实,Advagraf将不再属于“me-too”药物范畴,而成为首选的免疫抑制剂。

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