Richens A, Banfield C R, Salfi M, Nomeir A, Lin C C, Jensen P, Affrime M B, Glue P
Cardiff Clinical Trials, Wales.
Br J Clin Pharmacol. 1997 Aug;44(2):129-34. doi: 10.1046/j.1365-2125.1997.00642.x.
The objective of this study was to compare the pharmacokinetics, safety and tolerability of the antiepileptic drug felbamate in young and elderly healthy vounteers.
The single and multiple dose pharmacokinetics of felbamate were examined in an open-label two-dose level parallel group study in 24 elderly (66 to 78-year-old) and 11 young (18 to 45-year-old) healthy volunteer subjects. Pharmacokinetics were determined from blood samples obtained over 120 h after administration of single 600 mg or 1200 mg doses, and after multiple doses of 600 mg or 1200 mg administered every 12 h. Safety and tolerability were assessed through laboratory tests, ECGs, vital signs and reported adverse events.
Single dose felbamate pharmacokinetic parameters differed between young and elderly subjects; compared with young subjects, elderly subjects had lower mean clearance (31.2 vs 25.1 ml min(-1); 90% CI -11.4 to -0.9; P = 0.02) and a trend towards a greater half-life (18.6 vs 21.0 h; 90% CI -0.6 to 5.4; P = 0.11). Mean AUC and C(max) values were also higher in elderly subjects. No gender differences were noted for weight-adjusted pharmacokinetic variables. Felbamate was less well tolerated in elderly subjects compared with young subjects, as shown by higher rates of adverse event reporting and dropouts at the higher dose level. This may be due to age-related pharmacokinetic differences, to the rapid dose titration schedule used in this study, and/or to altered sensitivity to felbamate's pharmacodynamic effects.
These findings imply that elderly subjects require lower initial dosing and slower dose titration of felbamate than non-elderly subjects.
本研究的目的是比较抗癫痫药物非氨酯在年轻和老年健康志愿者中的药代动力学、安全性和耐受性。
在一项开放标签的两剂量水平平行组研究中，对24名老年（66至78岁）和11名年轻（18至45岁）健康志愿者进行了非氨酯的单剂量和多剂量药代动力学研究。在单次服用600mg或1200mg剂量以及每12小时多次服用600mg或1200mg剂量后120小时内采集血样，测定药代动力学。通过实验室检查、心电图、生命体征和报告的不良事件评估安全性和耐受性。
年轻和老年受试者单剂量非氨酯的药代动力学参数不同；与年轻受试者相比，老年受试者的平均清除率较低（31.2对25.1ml·min⁻¹；90%CI -11.4至-0.9；P = 0.02），半衰期有延长趋势（18.6对21.0小时；90%CI -0.6至5.4；P = 0.11）。老年受试者的平均AUC和C(max)值也较高。体重校正的药代动力学变量未观察到性别差异。与年轻受试者相比，老年受试者对非氨酯的耐受性较差，高剂量水平的不良事件报告率和退出率较高。这可能是由于年龄相关的药代动力学差异、本研究中使用的快速剂量滴定方案和/或对非氨酯药效学作用的敏感性改变。
这些发现表明，与非老年受试者相比，老年受试者使用非氨酯时需要更低的初始剂量和更慢的剂量滴定。
