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器官移植后他克莫司从速释或缓释剂型转换为控释剂型后的患者内变异性

Tacrolimus Intrapatient Variability After Switching From Immediate or Prolonged-Release to Extended-Release Formulation, After an Organ Transplantation.

作者信息

Del Bello Arnaud, Gaible Clotilde, Longlune Nathalie, Hebral Anne-Laure, Esposito Laure, Gandia Peggy, Kamar Nassim

机构信息

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.

出版信息

Front Pharmacol. 2021 Oct 7;12:602764. doi: 10.3389/fphar.2021.602764. eCollection 2021.

Abstract

Several formulations of tacrolimus are available, but evidence of the benefit of changing to the most recent formulations is lacking. Tacrolimus intra-patient variability (tacrolimus IPV) is an emerging risk factor associated with poor graft outcomes after solid organ transplantations. Here, we examined the modifications of tacrolimus IPV after switching to a different formulation of tacrolimus. We identified 353 solid organ transplant recipients that were switched in our center from immediate-release (IR-tacrolimus) or prolonged-release tacrolimus (PR-tacrolimus) to extended-release, LCP-tacrolimus (LCP-tacrolimus). Among them, 54 patients underwent at least 3 available tacrolimus blood concentrations before and after the switch, allowing us to investigate tacrolimus IPV. The switch was considered as a safe procedure since only four of the 353 patients presented a graft rejection after the switch, and no patient was hospitalized for tacrolimus overdose. The tacrolimus IPV estimated by the coefficient of variation (CV-IPV) was stable before and after the switch to LCP-tacrolimus (CV-IPV: 29.0% (IQR 25-75 (15.5; 38.5) before and 24.0% (15.8; 36.5) after the switch, p = 0.65). and Implications Switching from IR- or PR-tacrolimus to LCP-tacrolimus is a safe procedure. However, the CV-tacrolimus IPV was not impacted by the change of formulation.

摘要

他克莫司有多种剂型,但尚无证据表明更换为最新剂型会带来益处。他克莫司个体内变异性(他克莫司IPV)是实体器官移植后移植物预后不良的一个新出现的危险因素。在此,我们研究了更换他克莫司剂型后他克莫司IPV的变化情况。我们确定了353例实体器官移植受者,这些患者在我们中心从速释型他克莫司(IR-他克莫司)或缓释型他克莫司(PR-他克莫司)转换为长效缓释型他克莫司(LCP-他克莫司)。其中,54例患者在转换前后至少有3次可用的他克莫司血药浓度,这使我们能够研究他克莫司IPV。转换被认为是一个安全的过程,因为353例患者中只有4例在转换后出现了移植物排斥反应,且没有患者因他克莫司过量住院。转换为LCP-他克莫司前后,通过变异系数估计的他克莫司IPV(CV-IPV)是稳定的(CV-IPV:转换前为29.0%(IQR 25-75(15.5;38.5)),转换后为24.0%(15.8;36.5),p = 0.65)。结论从IR-他克莫司或PR-他克莫司转换为LCP-他克莫司是一个安全的过程。然而,剂型的改变并未影响他克莫司的CV-IPV。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b5/8529208/771da41a57c4/fphar-12-602764-g001.jpg

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