Shire Development LLC, Wayne, PA.
Neuropsychiatr Dis Treat. 2013;9:219-29. doi: 10.2147/NDT.S38377. Epub 2013 Feb 12.
Pharmacokinetic and safety data on stimulants in older adults are limited. The objective of this study was to characterize the pharmacokinetics of lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, in older adults.
In this two-period crossover trial, healthy adults (n = 47) stratified by age (55-64, 65-74, and ≥ 75 years) and gender received randomized, double-blind, single doses of LDX 50 mg or placebo. Baseline creatinine clearance, d-amphetamine and intact LDX pharmacokinetics, and safety were assessed.
Mean (±standard deviation) baseline creatinine clearance in participants aged 55-64, 65-74, and ≥ 75 years was 102.5 ± 26.1, 105.3 ± 23.1, and 94.9 ± 27.3 mL per minute, respectively. In the groups aged 55-64, 65-74, and ≥ 75 years, the mean maximum plasma d-amphetamine concentration in men was 44.2 ± 11.1, 47.7 ± 7.0, and 53.4 ± 19.4 ng/mL, respectively; area under the concentration time curve from time 0 extrapolated to infinity (AUC(0-inf)) was 915.0 ± 164.9, 1123.0 ± 227.0, and 1325.0 ± 464.4 nghour/mL; median time to reach peak plasma concentration was 4.5, 3.5, and 5.5 hours; in women, mean maximum plasma d-amphetamine concentration was 51.0 ± 6.7, 50.2 ± 6.8, and 64.3 ± 12.1 ng/mL, AUC(0-inf) was 1034.5 ± 154.6, 988.4 ± 80.5, and 1347.8 ± 198.9 ng hour/mL, and median time to reach peak plasma concentration was 3.5, 4.1, and 5.5 hours, respectively. d-Amphetamine clearance was unrelated to baseline creatinine clearance. Five participants aged 55-64 years reported treatment-emergent adverse events (versus one each aged 65-74 and ≥ 75 years), and as did six women (versus one man). No trends in blood pressure or pulse changes were seen with LDX according to age. In participants aged 55-64, 65-74, and ≥ 75 years, the mean change from time-matched baseline pulse ranged from -5.0 to 14.7, -4.3 to 9.5, and -3.0 to 14.7 beats per minute; for systolic blood pressure, from -3.9 to 18.5 mmHg, -2.1 to 14.5 mmHg, and -5.9 to 16.0 mmHg; for diastolic blood pressure from -2.5 to 8.3 mmHg, from -0.8 to 9.4 mmHg, and -0.6 to 9.5 mmHg. Vital sign changes were similar between men and women.
Clearance of d-amphetamine decreased with age and was unrelated to creatinine clearance. No trends in pulse or blood pressure changes with LDX were seen according to age. The safety profile of LDX was consistent with prior observations in younger adult study participants.
关于老年人兴奋剂的药代动力学和安全性数据有限。本研究的目的是描述长半衰期苯丙胺前药 lisdexamfetamine dimesylate（LDX）在老年人中的药代动力学特征。
在这项 2 期交叉试验中，根据年龄（55-64 岁、65-74 岁和≥75 岁）和性别分层的健康成年人（n=47）接受了随机、双盲、单次剂量的 LDX 50mg 或安慰剂。评估了基线肌酐清除率、d-苯丙胺和完整 LDX 的药代动力学以及安全性。
55-64 岁、65-74 岁和≥75 岁参与者的平均（±标准差）基线肌酐清除率分别为 102.5±26.1、105.3±23.1 和 94.9±27.3mL/min。在 55-64 岁、65-74 岁和≥75 岁组中，男性的最大血浆 d-苯丙胺浓度的平均值分别为 44.2±11.1、47.7±7.0 和 53.4±19.4ng/mL；从时间 0 外推至无穷大的浓度时间曲线下面积（AUC（0-inf））分别为 915.0±164.9、1123.0±227.0 和 1325.0±464.4ng·h/mL；达到最大血浆浓度的中位数时间分别为 4.5、3.5 和 5.5 小时；女性的平均最大血浆 d-苯丙胺浓度分别为 51.0±6.7、50.2±6.8 和 64.3±12.1ng/mL，AUC（0-inf）分别为 1034.5±154.6、988.4±80.5 和 1347.8±198.9ng·h/mL，达到最大血浆浓度的中位数时间分别为 3.5、4.1 和 5.5 小时。d-苯丙胺清除率与基线肌酐清除率无关。5 名 55-64 岁的参与者报告了治疗相关的不良事件（而 65-74 岁和≥75 岁的参与者各有 1 名），6 名女性（而 1 名男性）也报告了治疗相关的不良事件。根据年龄，LDX 没有导致血压或脉搏变化的趋势。在 55-64 岁、65-74 岁和≥75 岁的参与者中，从时间匹配的基线脉搏的平均变化范围为-5.0 至 14.7、-4.3 至 9.5 和-3.0 至 14.7 次/分钟；收缩压的变化范围为-3.9 至 18.5mmHg、-2.1 至 14.5mmHg 和-5.9 至 16.0mmHg；舒张压的变化范围为-2.5 至 8.3mmHg、-0.8 至 9.4mmHg 和-0.6 至 9.5mmHg。男性和女性的生命体征变化相似。
d-苯丙胺的清除率随年龄增长而降低，与肌酐清除率无关。根据年龄，LDX 对脉搏或血压变化没有趋势。LDX 的安全性与年轻成年参与者的先前观察结果一致。
