Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C):: Characterization by dynamic liver function tests
Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C):: Characterization by dynamic liver function tests
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DOI：
10.1016/j.clpt.2005.02.003
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发表时间：
2005-06-01
影响因子：
6.7
通讯作者：
Roots, I
中科院分区：
文献类型：
--
作者：
Brockmöller, J;Thomsen, T;Roots, I
背景：左乙拉西坦是一种抗癫痫药物，被批准用于成人部分性发作癫痫的持续治疗。我们试图研究左乙拉西坦及其代谢产物ucb L057在肝硬化患者中的药代动力学可能发生的变化，这些患者可能需要调整剂量。5名健康受试者和Child-Pugh A级（n = 5）、B级（n = 6）或C级（n = 5）酒精性肝硬化患者接受左乙拉西坦单次给药。测定左乙拉西坦和ucb L057的药代动力学，并将其与生化肝功能参数、肌酐清除率以及咖啡因、利多卡因和D-山梨醇的动力学作为特异性肝功能的探针进行相关性分析。动态肝功能检查显示肝功能恶化。左乙拉西坦及其代谢产物的药代动力学在健康受试者和A级或B级肝硬化受试者之间没有差异。然而，在C级肝硬化患者中，左乙拉西坦总清除率降低了57%（90%置信区间[CI]，43%-67%; P <0.01）。Child-Pugh C级左乙拉西坦与对照组的血浆浓度-时间曲线下面积的几何平均值比值为2.41（90% CI，1.80-3.23），半衰期比值的几何平均值为2.27（90% CI，1.74-2.97）。这是解释了严重的肝diseases.Conclusions患者的肾功能恶化：在肝损害的药代动力学研究，包括所有类别的肝硬化可能比只包括选定的类别的肝衰竭更揭示。轻度至中度肝损害患者无需调整左乙拉西坦剂量;然而，重度肝硬化患者最初仅应接受通常推荐剂量的一半。
Background: Levetiracetam is an antiepileptic drug approved for use as adjunctive therapy in adults with partial-onset seizures. We sought to investigate possible changes in the pharmacokinetics of levetiracetam and its metabolite ucb L057 in patients with liver cirrhosis, who may require dose adjustments.Methods. A single dose of levetiracetam was administered to 5 healthy subjects and to patients with Child-Pugh class A (n = 5), B (n = 6), or C (n = 5) alcohol-induced cirrhosis. The pharmacokinetics of levetiracetam and ucb L057 was measured and correlated with biochemical liver function parameters, with creatinine clearance, and with kinetics of caffeine, lidocaine, and D-sorbitol as probes for specific liver functions.Results. Dynamic liver function tests revealed a deterioration of liver function. The pharmacokinetics of levetiracetam and its metabolite did not differ between healthy subjects and those with class A or B cirrhosis. However, in patients with class C cirrhosis, levetiracetam total clearance was reduced by 57% (90% confidence interval [CI], 43%-67%; P < 001). The geometric mean ratio of the area under the plasma concentration-time curve for levetiracetam, Child-Pugh class C versus control, was 2.41 (90% CI, 1.80-3.23), and the geometric mean of the half-life ratio was 2.27 (90% CI, 1.74-2.97). This was explained by the deterioration of renal function in patients with severe hepatic disease.Conclusions: In pharmacokinetic studies of hepatic impairment, including all classes of cirrhosis may be more revealing than including only selected classes of liver failure. No dose adjustment of levetiracetam is necessary in patients with mild to moderate liver impairment; however, patients with severe cirrhosis should initially receive only half of the commonly recommended dose.