Zakrzewska Alicja, Kuczyńska Julita, Dermanowski Michał, Wyszogrodzka Edyta, Dominiak Monika, Mierzejewski Paweł
Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland.
Basic Clin Pharmacol Toxicol. 2020 Jan;126(1):51-58. doi: 10.1111/bcpt.13292. Epub 2019 Aug 12.
Measurement of hair drug content may be a reliable biomarker of the history of drug exposure, allowing to assess patient long-term compliance. Studies on correlations between antiepileptic drugs intake and their hair contents are limited. The aim of the study was to determine the association between the history of levetiracetam administration and its content in rat hair in controlled laboratory conditions. Additionally, the effects of levetiracetam on hair growth rate and body-weights were examined. Three groups of 12 rats each were exposed to different schedules of levetiracetam administration (10 mg/kg i.p.: every 24, 48 and 72 hours) for 30 days. The control group received daily saline injection. Levetiracetam concentrations in hair were assessed by validated LC-MS/MS method. The mean hair concentrations were as follows: 300 (±100), 170 (±60) and 130 (±80) ng/mg for rats receiving levetiracetam every 24, 48 and 72 hours, respectively. The levetiracetam accumulation in the hair was correlated with the total number of doses received (r = .699, P < .001). Levetiracetam did not affect the hair growth rate and rat body-weight. The concentration of levetiracetam measured in rat hair represents a reliable marker. It may reflect the adherence to levetiracetam treatment; however, further studies on human beings are needed.
测量毛发中的药物含量可能是药物暴露史的可靠生物标志物，有助于评估患者的长期依从性。关于抗癫痫药物摄入量与其毛发含量之间相关性的研究有限。本研究的目的是在可控的实验室条件下确定左乙拉西坦给药史与其在大鼠毛发中的含量之间的关联。此外，还研究了左乙拉西坦对毛发生长速率和体重的影响。将三组大鼠，每组12只，分别按照不同的给药方案（10mg/kg腹腔注射：每24、48和72小时一次）给予左乙拉西坦，持续30天。对照组每日注射生理盐水。采用经过验证的液相色谱-串联质谱法（LC-MS/MS）评估毛发中的左乙拉西坦浓度。毛发中的平均浓度如下：每24、48和72小时接受一次左乙拉西坦的大鼠，其毛发中左乙拉西坦浓度分别为300（±100）、170（±60）和130（±80）ng/mg。毛发中左乙拉西坦的蓄积量与接受的总剂量数相关（r = 0.699，P < 0.001）。左乙拉西坦不影响毛发生长速率和大鼠体重。在大鼠毛发中测得的左乙拉西坦浓度是一个可靠的标志物。它可能反映了对左乙拉西坦治疗的依从性；然而，还需要对人类进行进一步研究。
