Department of Clinical Pharmacy, Hospital General Universitario de Castellón, Castellon, Spain.
Eur J Hosp Pharm. 2020 Mar;27(e1):e2-e6. doi: 10.1136/ejhpharm-2018-001616. Epub 2018 Oct 20.
Although levetiracetam presents an easy dosing and tolerability, therapeutic drug monitoring may be recommended in certain situations. Measurement of levetiracetam in serum plasma is commonly done by high performance liquid chromatography (HPLC). After ARK Diagnostics marketed an enzyme immunoassay (IA) for levetiracetam in serum or plasma, automated determinations are possible. In this study, the performance of this immunoassay and the impact of automation on the follow-up in patients treated with levetiracetam is evaluated. We also detected those subpopulations of patients who may benefit the most from this therapeutic drug monitoring.
Samples from 50 outpatients diagnosed with epilepsy and treated with levetiracetam were collected. This new IA was performed on the Architect c4000 analyser and compared with the HPLC. Then, a retrospective observational study that included serum samples of levetiracetam for 24 months, was conducted to evaluate the impact of automattion and the influence of some variables (age, sex, renal function, and co-administration of valproic acid and glucuronidation-inducing drugs) in levetiracetam apparent oral clearance (CLp/F) by a multivariate linear regression.
The mean high-performance liquid chromatography quantified concentration (CpHPLC) was 18.43 mcg/mL (95% CI: 15.48 to 21.39) and immunoassay concentration (CpEI) was 18.35 mcg/mL (95% CI: 15.20 to 21.50) (P=0.861). The Pearson's linear correlation coefficient obtained in the analysis was r=0.88, according to the following equation: CpHPLC=-0.29+1.01 CpEI. The intraclass correlation coefficient was 0.95 (95% CI: 0.91 to 0.97). After IA implementation, the number of levetiracetam determinations increased in 76.27%. The median of Clp/F was higher (P<0.001) in inducers (4.36 L/h; IQR:3.29-5.44) and lower (P<0.001) in glomerular filtration rate (GFR) <60 mL/min (2.7 L/h; IQR: 0.58-3.85).
The Ark method performed on the Architect is fully acceptable and can be used routinely to measure levetiracetam plasmatic concentration levels. It has demonstrated the need for closer monitoring in patients with renal failure or co-administration of glucuronidation-inducing drugs.
虽然左乙拉西坦具有易于给药和良好的耐受性，但在某些情况下可能需要进行治疗药物监测。血清或血浆中的左乙拉西坦通常通过高效液相色谱法（HPLC）进行测量。在 ARK 诊断公司推出用于血清或血浆中的左乙拉西坦的酶免疫分析（IA）后，可实现自动化测定。在这项研究中，评估了这种免疫分析法的性能以及自动化对接受左乙拉西坦治疗的患者的随访的影响。我们还检测了那些可能最受益于这种治疗药物监测的患者亚群。
收集了 50 名被诊断患有癫痫并接受左乙拉西坦治疗的门诊患者的样本。在 Architect c4000 分析仪上进行新的 IA，并与 HPLC 进行比较。然后，进行了一项回顾性观察研究，该研究包括 24 个月的左乙拉西坦血清样本，通过多元线性回归评估自动化的影响以及某些变量（年龄、性别、肾功能以及与丙戊酸合用和葡萄糖醛酸诱导药物）对左乙拉西坦表观口服清除率（CLp/F）的影响。
高效液相色谱法定量浓度的平均值（CpHPLC）为 18.43 mcg/mL（95%CI：15.48 至 21.39），免疫分析浓度（CpEI）为 18.35 mcg/mL（95%CI：15.20 至 21.50）（P=0.861）。分析中获得的 Pearson 线性相关系数为 r=0.88，根据以下方程：CpHPLC=-0.29+1.01 CpEI。组内相关系数为 0.95（95%CI：0.91 至 0.97）。IA 实施后，左乙拉西坦的测定次数增加了 76.27%。诱导剂（4.36 L/h；IQR：3.29-5.44）的 Clp/F 中位数更高（P<0.001），肾小球滤过率（GFR）<60 mL/min（2.7 L/h；IQR：0.58-3.85）的 Clp/F 中位数更低（P<0.001）。
在 Architect 上进行的 Ark 方法完全可以接受，可常规用于测量左乙拉西坦的血浆浓度水平。它表明在肾功能衰竭或与葡萄糖醛酸诱导药物合用时，需要更密切地监测。
