增强的肾清除率会影响伴有和不伴有增强的肾清除率的创伤性脑损伤患者的左乙拉西坦浓度。

Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance.

机构信息

Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA.

Pharmacy Services UKHealthCare, Lexington, KY, USA.

出版信息

BMC Neurol. 2024 Jan 2;24(1):12. doi: 10.1186/s12883-023-03515-w.

DOI:10.1186/s12883-023-03515-w

PMID:38166710

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10759330/

Abstract

BACKGROUND

The purpose of this study was to examine the impact of ARC on levetiracetam concentrations during the first week following acute TBI. The hypothesis was levetiracetam concentrations are significantly lower in TBI patients with augmented renal clearance (ARC) compared to those with normal renal clearance.

METHODS

This is a prospective cohort pharmacokinetic study of adults with moderate to severe TBI treated with levetiracetam during the first week after injury. Serial blood collections were performed daily for analysis of levetiracetam, cystatin C, and 12-hr creatinine clearance (CrCl) determinations. Patients were divided into two cohorts: with (CrCl ≥130 ml/min/1.73 m) and without ARC.

RESULTS

Twenty-two patients with moderate to severe TBI were included. The population consisted primarily of young male patients with severe TBI (mean age 40 years old, 68% male, median admission GCS 4). Each received levetiracetam 1000 mg IV every 12 h for the study period. ARC was present in 77.3% of patients, with significantly lower levetiracetam concentrations in ARC patients and below the conservative therapeutic range (< 6mcg/mL) for all study days. In patients without ARC, the serum concentrations were also below the expected range on all but two study days (Days 4 and 5). Four of the 22 (18.2%) patients exhibited seizure activity during the study period (two of these patients exhibited ARC). Cystatin C concentrations were significantly lower in patients with ARC, though the mean for all patients was within the typical normal range.

CONCLUSIONS

ARC has a high prevalence in patients with moderate to severe TBI. Levetiracetam concentrations after standard dosing were low in all TBI patients, but significantly lower in patients with ARC. This study highlights the need to consider personalized drug dosing in TBI patients irrespective of the presence of ARC.

CLINICAL TRIAL REGISTRATION

This study was registered at cliicaltrials.gov (NCT02437838) Registered on 08/05/2015, https://clinicaltrials.gov/ct2/show/NCT02437838 .

摘要

背景

本研究旨在探讨急性创伤性脑损伤（TBI）后第一周 ARC 对左乙拉西坦浓度的影响。假设是伴有增强肾清除率（ARC）的 TBI 患者的左乙拉西坦浓度明显低于正常肾清除率的患者。

方法

这是一项对接受左乙拉西坦治疗的中度至重度 TBI 成人进行的前瞻性队列药代动力学研究。在损伤后第一周内每天进行多次血样采集，以分析左乙拉西坦、胱抑素 C 和 12 小时肌酐清除率（CrCl）的测定值。患者分为两组：有（CrCl≥130 ml/min/1.73 m）和无 ARC。

结果

纳入了 22 例中度至重度 TBI 患者。该人群主要由年轻男性严重 TBI 患者组成（平均年龄 40 岁，68%为男性，入院时 GCS 中位数为 4）。每位患者在研究期间均接受 1000 mg IV 左乙拉西坦，每 12 小时一次。77.3%的患者存在 ARC，ARC 患者的左乙拉西坦浓度明显较低，且所有研究日均低于保守治疗范围（<6mcg/mL）。在无 ARC 的患者中，除了两天（第 4 天和第 5 天）外，其余所有研究日的血清浓度也低于预期范围。22 例患者中有 4 例（18.2%）在研究期间出现癫痫发作（其中 2 例有 ARC）。有 ARC 的患者胱抑素 C 浓度明显较低，尽管所有患者的平均值均在典型正常范围内。