Herron J, Lee P, Pesco-Koplowitz L, Gajjar D, Soo Y W, Woestenborghs R
Arkansas Research Medical Testing Center, Little Rock, USA.
Clin Ther. 1998 Jul-Aug;20(4):682-90. doi: 10.1016/s0149-2918(98)80131-8.
The dose proportionality of lubeluzole, a drug in clinical development for the treatment of acute ischemic stroke, was evaluated in a Phase I, single-center, open-label, randomized-dosing-sequence, three-way crossover clinical trial in 12 healthy adults. An equal number of male and female volunteers were enrolled in the trial, with a mean weight (+/- SD) of 73.2 +/- 11.9 kg, mean height (+/- SD) of 66.8 +/- 4.6 inches, and a mean age of 36.1 +/- 5.2 years. Subjects received intravenous infusions of 5 (A), 10 (B), and 15 mg (C) of lubeluzole over 1 hour on three separate occasions, with a minimum washout period of 2 weeks. The treatment sequences were A-B-C; A-C-B; B-A-C; B-C-A; C-A-B; and C-B-A. One male and one female were assigned to each sequence. After the 5-, 10-, and 15-mg doses, maximum concentration (Cmax) was 58.1, 113, and 138 microg/L, respectively, and the area under the curve from 0 to (AUC(0-infinity)) was 771, 1384, and 2025 microg x h/L. There were no statistically significant differences among the groups in mean terminal half-life, steady-state volume of distribution, total plasma clearance, or dose-normalized AUC(0-infinity). Dose-normalized values of Cmax differed significantly between the groups. No serious adverse events were reported, and no changes were observed in cardiac function, as judged by the QT(c) interval. The pharmacokinetics of lubeluzole appear to be linear at intravenous infusion doses of 5, 10, and 15 mg, and these doses are well tolerated by healthy adults.
卢比替定是一种正处于急性缺血性中风治疗临床开发阶段的药物，其剂量比例性在一项I期单中心、开放标签、随机给药顺序、三向交叉临床试验中对12名健康成年人进行了评估。试验招募了数量相等的男性和女性志愿者，平均体重（±标准差）为73.2±11.9千克，平均身高（±标准差）为66.8±4.6英寸，平均年龄为36.1±5.2岁。受试者在三个不同场合分别接受了1小时内静脉输注5毫克（A）、10毫克（B）和15毫克（C）的卢比替定，最短洗脱期为2周。治疗顺序为A-B-C；A-C-B；B-A-C；B-C-A；C-A-B；以及C-B-A。每个顺序分配一名男性和一名女性。在5毫克、10毫克和15毫克剂量后，最大浓度（Cmax）分别为58.1、113和138微克/升，从0到无穷大的曲线下面积（AUC(0-∞)）分别为771、1384和2025微克·小时/升。各组在平均终末半衰期、稳态分布容积、总血浆清除率或剂量标准化的AUC(0-∞)方面无统计学显著差异。Cmax的剂量标准化值在各组之间存在显著差异。未报告严重不良事件，根据QT(c)间期判断，心脏功能未观察到变化。卢比替定在5毫克、10毫克和15毫克静脉输注剂量下的药代动力学似乎呈线性，且这些剂量在健康成年人中耐受性良好。
