Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy
Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy
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DOI：
10.1212/01.wnl.0000316392.55784.57
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发表时间：
2008-07-01
期刊：
影响因子：
9.9
通讯作者：
Leppik, I. E.
中科院分区：
文献类型：
--
作者：
Ahn, J. E.;Cloyd, J. C.;Leppik, I. E.
背景资料：苯妥英钠（Phenytoin，PHT）被广泛用于老年癫痫的治疗，但其在老年癫痫患者中的药代动力学研究资料有限。目的：本研究的目的是探讨年龄和性别对PHT的药代动力学的影响。受试者为18岁或以上癫痫患者，但其他方面健康，接受PHT维持方案，未服用相互作用药物。受试者单次注射100 mg剂量的SL-PHT或SL-FOS，然后按常规早晨PHT剂量低于100 mg。在SL给药后196小时内采集系列血样。血浆PHT和SL-PHT浓度通过气相色谱-质谱法测定。PHT药代动力学的特点是使用人口为基础的，非线性，mixed-effects model.Results：63名受试者完成了研究，其中45人是65岁或以上。在PHT清除率、分布容积和消除半衰期方面，成人与老年人或男性与女性之间无差异。平均消除半衰期为40 hours.Conclusions：健康的老年人似乎有相同的苯妥英（PHT）的药代动力学作为年轻的成年人。减少PHT剂量需求可能是由于患者对药物治疗和毒性作用的敏感性的年龄相关变化。延长的消除半衰期表明，大多数患者可以每天服用一次PHT，达到稳态的时间可能延长至2-3周。
Background: Phenytoin (PHT) is widely used to treat epilepsy in elderly patients, but information on its pharmacokinetics in this population is limited.Objective: The purpose of this study was to investigate the effects of age and sex on PHT pharmacokinetics using stable-labeled (SL) isotopes of PHT or fosphenytoin (FOS) administered IV or IM while patients remained on their oral maintenance regimen.Methods: Subjects were patients 18 years or older with epilepsy, but otherwise healthy, on a maintenance regimen of PHT who were not taking interacting medications. Subjects were given a single injection of a 100 mg dose of SL-PHT or SL-FOS followed by their usual morning PHT dose less 100 mg. Serial blood samples were collected up to 196 hours after the SL dose. Plasma PHT and SL-PHT concentrations were measured by a gas chromatographic-mass spectrometric assay. PHT pharmacokinetics were characterized using a population-based, nonlinear, mixed-effects model.Results: Sixty-three subjects completed the study, 45 of whom were 65 years or older. There was no difference between adult and elderly or men and women in PHT clearance, distribution volume, and elimination half-life. The mean elimination half-life was 40 hours.Conclusions: Healthy elderly adults appear to have the same phenytoin ( PHT) pharmacokinetics as younger adults. Reduced PHT dosage requirements may be due to age-related changes in patients' sensitivity to the therapeutic and toxic effects of the drug. The prolonged elimination half-life suggests that most patients can take PHT once daily and the time to reach steady-state may extend to 2-3 weeks.