Pregabalin pharmacology and its relevance to clinical practice
Pregabalin pharmacology and its relevance to clinical practice
复制标题
DOI：
10.1111/j.0013-9580.2004.455003.x
复制
发表时间：
2004-01-01
期刊：
影响因子：
5.6
通讯作者：
Ben-Menachem, E
中科院分区：
文献类型：
--
作者：
Ben-Menachem, E
普瑞巴林是中枢神经系统电压门控钙通道α-2-δ亚基的有效配体，在一系列动物模型中表现出强效抗惊厥、镇痛和抗焦虑活性。此外，在临床试验中，普瑞巴林已被证明是部分性癫痫发作的高效预防性治疗。与α-2-δ位点的有效结合减少了去极化诱导的钙内流，从而调节兴奋性神经递质的释放。普瑞巴林对GABA能机制无明显影响。普瑞巴林表现出高度可预测性和线性药代动力学，这一特征使其易于在临床实践中使用。吸收广泛、迅速，并与剂量成比例。达到最大血药浓度的时间与1小时相似，在24-48小时内达到稳态。这些特征反映了在临床试验中早在第2天观察到的疗效起效。高生物利用度、6.3 h的平均消除半衰期（t（1/2））以及与剂量成比例的最大血浆浓度和总暴露量预测了临床实践中的剂量-反应关系，并允许临床实践中的有效起始剂量为150 mg/天，无需滴定。与食物一起给药对普瑞巴林的吸收量没有临床相关影响，提供了一种不受食物影响的给药方案。普瑞巴林不与血浆蛋白结合，几乎以不变的形式排泄（
Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. In addition, pregabalin has been shown to be a highly effective adjunctive therapy for partial seizures in clinical trials. Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. Pregabalin demonstrates highly predictable and linear pharmacokinetics, a profile that makes it easy to use in clinical practice. Absorption is extensive, rapid, and proportional to dose. Time to maximal plasma concentration is similar to1 h and steady state is achieved within 24-48 h. These characteristics reflect the observed onset of efficacy as early as day two in clinical trials. High bioavailability, a mean elimination half life (t(1/2)) Of 6.3 h, and dose-proportional maximal plasma concentrations and total exposures predict a dose-response relationship in clinical practice and allow an effective starting dose of 150 mg/day in clinical practice without need for titration. Administration with food has no clinically relevant effect on the amount of pregabalin absorbed, providing for a dosing regimen uncomplicated by meals. Pregabalin does not bind to plasma proteins and is excreted virtually unchanged (