Influence of Sex, Age, and Weight on Levetiracetam Pharmacokinetics
Influence of Sex, Age, and Weight on Levetiracetam Pharmacokinetics
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DOI：
10.1097/ftd.0000000000000550
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发表时间：
2018-10-01
影响因子：
2.5
通讯作者：
Aldaz, Azucena
中科院分区：
文献类型：
--
作者：
Alzueta, Natalia;Ortega, Ana;Aldaz, Azucena
背景：左乙拉西坦（LEV）是广泛用于治疗的第二代抗癫痫药物。本研究的目的是评估临床实践中性别、年龄和体重对LEV药代动力学的影响。方法：我们进行了为期6年的回顾性观察研究。根据性别、体重（正常范围、超重和肥胖）和年龄（青年：16-30岁，中年：31-50岁，老年：51-64岁，老年：≥65岁）将患者分为亚组。我们比较了亚组之间的 LEV 表观口腔清除率 (LEV CL/F)。结果：共鉴定出对应于 156 名患者的 238 个 LEV 基础血清浓度 (LEV C-0)。当 LEV CL/F 表示为 L/h 时，男性和女性之间的 LEV CL/F 存在显着差异[平均值 (SD)：男性为 4.79 (1.84) L/h，女性为 4.13 (1.64) L/h； P<0.001]。当 LEV CL/F 按体重标准化时，这些差异并不显着 [平均值 (SD)：男性为 60.64 (24.90) mL/h/kg，女性为 64.10 (28.87) mL/h/kg；名词s.]。女性体重比男性低 17%。随着年龄的增长，LEV CL/F 逐渐降低，其比例与肾功能下降的比例相似。与成人相比，老年患者的 LEV CL/F (mL/h/kg) 降低 30%，肌酐清除率 (CCr) 降低 43%。体重亚组之间以 L/h 计算的 LEV CL/F 没有观察到统计学上的显着差异。然而，当LEV CL/F以mL/h/kg表示时，观察到逐渐降低[正常体重：72.21（28.97）；超重：57.84（25.38）；肥胖：49.45 (14.50)； P<0.001]。观察到CCr和LEV CL/F之间存在显着的正相关性，证实了肾功能在LEV CL/F中的重要作用。当体重增加时，每个性别组的 CCr 都会增加；然而，LEV CL/F (L/h) 保持不变。结论：性别、年龄和体重影响 LEV 药代动力学，对实现治疗目标所需的个体剂量方案产生影响。性别是 LEV CL/F 的一个调节因素，尽管其影响主要是由于体重。 LEV CL/F 随着年龄的增长而降低，与肾功能的下降成比例。已证实，不需要按体重计算 LEV 剂量，并且在肥胖患者中开出更高剂量的 LEV 是没有道理的。这些数据表明，老年患者、肾功能不全患者和肥胖患者需要进行常规 LEV 治疗药物监测。
Background: Levetiracetam (LEV) is a second-generation antiepileptic drug extensively used in therapeutics. The aim of this study was to evaluate the influence that sex, age, and weight exert on LEV pharmacokinetics in clinical practice.Methods: We conducted a 6-year retrospective observational study. Patients were classified in subgroups according to sex, weight (normal range, overweight, and obese), and age (young adult: 16-30 years old, middle-aged adult: 31-50 years old, advanced adult: 51-64 years old, and elderly adult: >= 65 years old). We compared LEV apparent oral clearance (LEV CL/F) between the subgroups.Results: A total of 238 LEV basal serum concentrations (LEV C-0) corresponding to 156 patients were identified. Significant differences were observed in LEV CL/F between males and females when LEV CL/F was expressed as L/h [mean (SD): 4.79 (1.84) L/h in males versus 4.13 (1.64) L/h in females; P < 0.001]. These differences were not significant when LEV CL/F was normalized by weight [mean (SD): 60.64 (24.90) mL/h/kg in males versus 64.10 (28.87) mL/h/kg in females; n. s.]. Weight in females was 17% lower compared with males. A progressive reduction in LEV CL/F was observed with increasing age, in a proportion that was similar to the decline in renal function. The elderly patients presented 30% lower LEV CL/F (mL/h/kg) and 43% lower creatinine clearance (CCr) in comparison with adults. No statistically significant differences were observed in LEV CL/F calculated in L/h between weight subgroups. However, when LEV CL/F was expressed in mL/h/kg, a progressive reduction was observed [normal weight: 72.21 (28.97); overweight: 57.84 (25.38); obese: 49.45 (14.50); P < 0.001]. A significant and positive correlation between CCr and LEV CL/F was observed, confirming the important role of the renal function in LEV CL/F. The CCr increased in each sex group when weight increased; however, LEV CL/F (L/h) remained constant.Conclusions: Sex, age, and weight affect LEV pharmacokinetics, having an impact on the individual dosage regimen needed to achieve the therapeutic objective. Sex is a conditioning factor of LEV CL/F, although its influence is principally due to the weight. LEV CL/F decreases with advancing age, proportionally to the decline in renal function. It is confirmed that LEV dosage per body weight is not required, and prescribing higher doses of LEV in obese patients is not justified. These data suggest that routine LEV therapeutic drug monitoring in the elderly patients, patients with renal dysfunction, and obese patients is indicated.