Del Bello Arnaud, Gaible Clotilde, Longlune Nathalie, Hebral Anne-Laure, Esposito Laure, Gandia Peggy, Kamar Nassim
Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.
INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.
Front Pharmacol. 2021 Oct 7;12:602764. doi: 10.3389/fphar.2021.602764. eCollection 2021.
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.
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。