Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
J Pharm Pharm Sci. 2018;21(1s):149s-176s. doi: 10.18433/jpps30081.
Levetiracetam (LEV) is a broad spectrum antiepileptic drug (AED) that has a more favorable side effect profile compared to older AEDs. Therapeutic drug monitoring (TDM) of LEV is generally unnecessary given its linear and predictable dose-serum concentration relationship, lack of drug-drug interactions, and broad therapeutic window. However, there is growing evidence showing that alteration of LEV pharmacokinetics (PK) may occur in special populations calling for the need for TDM. The purpose of this review was to summarize current literature surrounding altered LEV PK in special patient populations and determine if there is a need for levetiracetam TDM.
A literature search of MEDLINE (1946 - November 2017) database of available evidence pertaining to altered LEV PK in humans was conducted.
A total of 51 articles were found. There has not been a positive correlation shown between LEV levels and efficacy or toxicity. Variable LEV levels are reported in the literature with respect to adverse effects, seizures and efficacy occurring below, within and above the supposed reference ranges. Age is a major contributor to altered pharmacokinetics of LEV as shown in elderly patients and pediatric patients. Compared to adults, clearance of LEV has been shown to be decreased by almost half in patients over 65 and increased by 30-40% in pediatric patients. LEV pharmacokinetics varied further when data from its use in neonates was explored. LEV clearance declined in a linear fashion with declining estimates of creatinine clearance but was variable in patients with end-stage renal failure or those requiring renal replacement therapy. In patients who were critically ill, LEV clearance may be augmented and these patients may require higher doses of medications to maintain drug levels. In patients who are pregnant, LEV levels are likely to decline as pregnancy progresses due to changes in glomerular filtration rate and remain variable in the post-partum period.
Routine TDM of levetiracetam is not recommended for all populations, however, it may be beneficial to maintain an individual therapeutic range in patients where the PK of LEV may be altered, such as in patients who are critically ill patients, pregnant, pediatrics or elderly.
左乙拉西坦（LEV）是一种广谱抗癫痫药物（AED），与旧的 AED 相比，其具有更有利的副作用特征。鉴于 LEV 的线性和可预测的剂量-血清浓度关系、缺乏药物相互作用以及广泛的治疗窗口，通常不需要对其进行治疗药物监测（TDM）。然而，越来越多的证据表明，LEV 药代动力学（PK）的改变可能发生在特殊人群中，这需要进行 TDM。本综述的目的是总结有关特殊患者人群中 LEV PK 改变的现有文献，并确定是否需要 LEV 的 TDM。
对 MEDLINE（1946 年-2017 年 11 月）数据库中有关人类 LEV PK 改变的可用证据进行了文献检索。
共发现 51 篇文章。LEV 水平与疗效或毒性之间没有显示出正相关。文献中报道了与不良反应、癫痫发作和疗效相关的可变 LEV 水平，这些水平低于、处于和高于假定的参考范围。年龄是 LEV 药代动力学改变的主要因素，在老年患者和儿科患者中均有体现。与成年人相比，65 岁以上患者的 LEV 清除率几乎降低了一半，儿科患者的清除率增加了 30-40%。当探索 LEV 在新生儿中的使用数据时，LEV 药代动力学进一步变化。LEV 清除率呈线性下降，与估计的肌酐清除率下降相关，但在终末期肾病患者或需要肾脏替代治疗的患者中则各不相同。在危重患者中，LEV 清除率可能会增加，这些患者可能需要更高的药物剂量来维持药物水平。在孕妇中，随着妊娠的进展，LEV 水平可能会下降，因为肾小球滤过率发生了变化，并且在产后期间仍然变化不定。
不建议对所有人群常规进行 LEV 的 TDM，但对于 LEV PK 可能发生改变的患者（如危重症患者、孕妇、儿科或老年患者），维持个体化治疗范围可能会有所受益。
