Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration

IF 4.6 2区医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacokinetics Pub Date : 2024-04-06 DOI:10.1007/s40262-024-01368-1

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Abstract

Background and Objective

High variability in tacrolimus pharmacokinetics directly after lung transplantation (LuTx) may increase the risk for acute kidney injury (AKI) and transplant rejection. The primary objective was to compare pharmacokinetic variability in patients receiving tacrolimus orally versus intravenously early after LuTx.

Methods

Pharmacokinetic and clinical data from 522 LuTx patients transplanted between 2010 and 2020 in two university hospitals were collected to compare orally administered tacrolimus to intravenous tacrolimus early post-transplantation. Tacrolimus blood concentration variability, measured as intrapatient variability (IPV%) and percentage of time within the therapeutic range (TTR%), was analyzed within the first 14 days after LuTx. Secondary outcomes were AKI, acute rejection, length of stay in the intensive care unit (ICU), and mortality in the ICU and during hospital admission.

Results

We included 224 patients in the oral and 298 in the intravenous group. The mean adjusted IPV% was 10.8% (95% confidence interval [CI] 6.9–14.6; p < 0.001) higher in the oral group (27.2%) than the intravenous group (16.4%). The mean TTR% was 7.3% (95% CI − 11.3 to − 3.4; p < 0.001) lower in the oral group (39.6%) than in the intravenous group (46.9%). The incidence of AKI was 46.0% for oral and 42.6% for intravenous administration (adjusted odds ratio [OR] 1.2; 95% CI 0.8–1.8; p = 0.451). The frequencies of clinically diagnosed acute rejection in the oral and intravenous groups were nonsignificant (24.6% vs 17.8%; OR 1.5 [95% CI 1.0–2.3; p = 0.059]). ICU and hospital mortality rate and ICU length of stay were similar.

Conclusions

Administering tacrolimus orally directly after LuTx leads to a higher variability in blood concentrations compared to intravenous administration. There was no difference in the occurrence of AKI or transplant rejection.

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肺移植术后早期的他克莫司变异性和临床结果：口服与持续静脉给药

摘要背景和目的肺移植（LuTx）后直接服用他克莫司药代动力学的高变异性可能会增加急性肾损伤（AKI）和移植排斥反应的风险。主要目的是比较肺移植术后早期口服与静脉注射他克莫司患者的药代动力学变异性。方法收集了两家大学医院在 2010 年至 2020 年间移植的 522 例 LuTx 患者的药代动力学和临床数据，对移植后早期口服他克莫司和静脉注射他克莫司进行比较。分析了LuTx术后前14天内他克莫司血药浓度的变异性（以患者内变异性（IPV%）和治疗范围内时间百分比（TTR%）衡量）。次要结果包括：AKI、急性排斥反应、重症监护室（ICU）住院时间以及重症监护室和住院期间的死亡率。结果口服组有 224 名患者，静脉组有 298 名患者。口服组（27.2%）的平均调整后 IPV% 为 10.8%（95% 置信区间 [CI] 6.9-14.6；p < 0.001），高于静脉注射组（16.4%）。口服组（39.6%）的平均 TTR% 比静脉组（46.9%）低 7.3% (95% CI - 11.3 to - 3.4; p <0.001)。口服组 AKI 发生率为 46.0%，静脉注射组为 42.6%（调整赔率比 [OR] 1.2；95% CI 0.8-1.8；P = 0.451）。口服组和静脉注射组临床诊断急性排斥反应的频率差异不大（24.6% vs 17.8%；OR 1.5 [95% CI 1.0-2.3；p = 0.059]）。重症监护室和住院死亡率以及重症监护室住院时间相似。结论与静脉给药相比，LuTx术后直接口服他克莫司导致的血药浓度变化更大。AKI或移植排斥反应的发生率没有差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Pharmacokinetics 医学-药学

CiteScore

8.80

自引率

4.40%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.