背景:这项研究的目的是检查ARC对急性TBI后第一周左乙拉西坦浓度的影响。假设是左乙拉西坦浓度在肾清除率增强(ARC)的TBI患者中明显低于正常肾清除率的患者。
方法:这是一项前瞻性队列药代动力学研究,研究了伤后第一周内接受左乙拉西坦治疗的成人中度至重度TBI。每天进行连续采血以分析左乙拉西坦,胱抑素C,和12小时肌酐清除率(CrCl)测定。患者分为两组:有(CrCl≥130ml/min/1.73m2)和无ARC。
结果:纳入22例中度至重度TBI患者。人群主要是患有严重TBI的年轻男性患者(平均年龄40岁,68%男性,中位入院GCS4)。在研究期间,每个人每12小时接受左乙拉西坦1000mgIV。77.3%的患者存在ARC,在所有研究日,ARC患者的左乙拉西坦浓度显着降低,低于保守治疗范围(<6mcg/mL)。在没有ARC的患者中,除2个研究日(第4天和第5天)外,所有研究日的血清浓度均低于预期范围.在研究期间,22名患者中的4名(18.2%)表现出癫痫发作活动(这些患者中的2名表现出ARC)。ARC患者的胱抑素C浓度明显降低,尽管所有患者的平均值都在典型的正常范围内。
结论:ARC在中度至重度TBI患者中具有较高的患病率。在所有TBI患者中,标准给药后的左乙拉西坦浓度较低,但在ARC患者中明显降低。这项研究强调了无论是否存在ARC,TBI患者都需要考虑个性化药物给药。
背景:本研究在cliicaltrials.gov(NCT02437838)注册,注册于2015年8月5日,https://clinicaltrials.gov/ct2/show/NCT02437838。
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 m2) 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.
BACKGROUND: This study was registered at cliicaltrials.gov (NCT02437838) Registered on 08/05/2015, https://clinicaltrials.gov/ct2/show/NCT02437838 .