Levetiracetam is a second-generation antiepileptic drug, widely used in the treatment of focal and generalized epilepsy due to its pharmacokinetic and safety profiles. Its pharmacokinetic monitoring is ascribed as useful to personalize its dosing regimen. The aim of the present study was to describe, for the first time, the pharmacokinetics of levetiracetam in Portuguese refractory epileptic patients. Therefore, a retrospective study was carried out on 65 Portuguese refractory epileptic patients (pharmacokinetic study: 48; validation study: 17) admitted to the Refractory Epilepsy Centre of the Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. The pharmacokinetic parameters of levetiracetam were estimated by applying a one-compartment model with first-order absorption and elimination analysis. Male patients showed higher distribution volume (Vd/F) and oral clearance (CL/F) than female patients (median Vd/F: 52.40 L in males and 38.60 L in females, p = 0.011; median CL/F: 4.71 L/h in males and 3.91 L/h in females, p = 0.028). Higher values of Vd/F (p = 0.026) and CL/F (p = 0.003) were also found in overweight patients relative to normal weight and obese patients. Carbamazepine was the co-administered antiepileptic drug that mostly affected the pharmacokinetics of levetiracetam, increasing both Vd/F (61.30 L with carbamazepine and 39.10 L without carbamazepine, p = 0.007) and CL/F (6.71 L/h with carbamazepine and 3.91 L/h without carbamazepine, p < 0.001). The pharmacokinetics of levetiracetam was affected by gender, body mass index, and co-administration of carbamazepine. This study highlights the impact of several factors on the CL/ and Vd/F of levetiracetam when administered to refractory epileptic patients. The importance of its pharmacokinetic monitoring in clinical pharmacy stands out, thereby enabling the optimization of antiepileptic drug therapy.

中文翻译：

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左乙拉西坦在葡萄牙难治性癫痫患者中的药代动力学监测：性别，体重和伴随疗法的影响

左乙拉西坦是第二代抗癫痫药，由于其药代动力学和安全性特征，被广泛用于治疗局灶性和全身性癫痫。其药代动力学监测归因于个性化其给药方案。本研究的目的是首次描述左乙拉西坦在葡萄牙难治性癫痫患者中的药代动力学。因此，对葡萄牙科英布拉大学中心医院难治性癫痫中心收治的65例葡萄牙难治性癫痫患者进行了回顾性研究（药代动力学研究：48；验证研究：17）。左乙拉西坦的药代动力学参数通过应用具有一阶吸收和消除分析的单室模型进行估算。p = 0.011；中位CL / F：男性为4.71 L / h，女性为3.91 L / h，p = 0.028）。与正常体重和肥胖患者相比，超重患者的Vd / F（p = 0.026）和CL / F（p = 0.003）也较高。卡马西平是共同给药的抗癫痫药，主要影响左乙拉西坦的药代动力学，同时增加了Vd / F（卡马西平为61.30 L，无卡马西平为39.10 L，p = 0.007）和CL / F（卡马西平为6.71 L / h和3.91 L） / h（不含卡马西平），p<0.001）。左乙拉西坦的药代动力学受性别，体重指数和卡马西平共同给药的影响。这项研究着重介绍了难治性癫痫患者服用左乙拉西坦的CL /和Vd / F的几个因素的影响。其药代动力学监测在临床药学中的重要性突出，从而可以优化抗癫痫药物治疗。