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从标准释放剂型他克莫司转换为MeltDose他克莫司(LCPT)可改善肝移植后的肾功能。

Conversion from Standard-Release Tacrolimus to MeltDose Tacrolimus (LCPT) Improves Renal Function after Liver Transplantation.

作者信息

von Einsiedel Johannes, Thölking Gerold, Wilms Christian, Vorona Elena, Bokemeyer Arne, Schmidt Hartmut H, Kabar Iyad, Hüsing-Kabar Anna

机构信息

Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, 48149 Münster, Germany.

Department of Internal Medicine and Nephrology, University Hospital of Münster Marienhospital Steinfurt, 48565 Steinfurt, Germany.

出版信息

J Clin Med. 2020 Jun 1;9(6):1654. doi: 10.3390/jcm9061654.

Abstract

Renal impairment is a typical side effect of tacrolimus (Tac) treatment in liver transplant (LT) recipients. One strategy to avoid renal dysfunction is to increase the concentration/dose (C/D) ratio by improving drug bioavailability. LT recipients converted from standard-release Tac to MeltDose Tac (LCPT), a novel technological formulation, were able to reduce the required Tac dose due to higher bioavailability. Hence, we hypothesize that such a conversion increases the C/D ratio, resulting in a preservation of renal function. In the intervention group, patients were switched from standard-release Tac to LCPT. Clinical data were collected for 12 months after conversion. Patients maintained on standard-release Tac were enrolled as a control group. Twelve months after conversion to LCPT, median C/D ratio had increased significantly by 50% ( < 0.001), with the first significant increase seen 3 months after conversion ( = 0.008). In contrast, C/D ratio in the control group was unchanged after 12 months (1.75 vs. 1.76; = 0.847). Estimated glomerular filtration rate (eGFR) had already significantly deteriorated in the control group at 9 months (65.6 vs. 70.6 mL/min/1.73 m at study onset; = 0.006). Notably, patients converted to LCPT already had significant recovery of mean eGFR 6 months after conversion (67.5 vs. 65.3 mL/min/1.73 m at study onset; = 0.029). In summary, conversion of LT recipients to LCPT increased C/D ratio associated with renal function improvement.

摘要

肾功能损害是肝移植(LT)受者接受他克莫司(Tac)治疗的典型副作用。避免肾功能障碍的一种策略是通过提高药物生物利用度来提高浓度/剂量(C/D)比。从标准释放Tac转换为新型技术制剂MeltDose Tac(LCPT)的LT受者,由于生物利用度更高,能够减少所需的Tac剂量。因此,我们假设这种转换会提高C/D比,从而保护肾功能。在干预组中,患者从标准释放Tac转换为LCPT。转换后收集12个月的临床数据。继续使用标准释放Tac的患者作为对照组。转换为LCPT 12个月后,C/D比中位数显著增加了50%(<0.001),转换后3个月首次出现显著增加(=0.008)。相比之下,对照组12个月后的C/D比没有变化(1.75对1.76;=0.847)。对照组在9个月时估计肾小球滤过率(eGFR)已经显著恶化(研究开始时为65.6对70.6 mL/min/1.73 m²;=0.006)。值得注意的是,转换为LCPT的患者在转换6个月后平均eGFR已经有显著恢复(研究开始时为67.5对65.3 mL/min/1.73 m²;=0.029)。总之,LT受者转换为LCPT可提高C/D比并改善肾功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f02/7356524/66197c257aeb/jcm-09-01654-g001.jpg

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