Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects.
Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects.
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DOI：
10.3389/fphar.2017.00617
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发表时间：
2017
影响因子：
5.6
通讯作者：
Liechti ME
中科院分区：
文献类型：
--
作者：
Dolder PC;Strajhar P;Vizeli P;Hammann F;Odermatt A;Liechti ME
理由：利地安非他明是d -安非他明的前药，用于治疗注意力缺陷/多动障碍（ADHD）。与口服d -安非他明相比，利地安非他明被认为具有较长的药代动力学特征，可能与较低的药物喜好和较低的口服滥用风险有关。然而，利地安非他明和d -安非他明在药代动力学和药效学上的差异尚未被直接比较。方法：在一项随机、双盲、安慰剂对照的交叉研究中，对24名健康受试者给予等摩尔剂量的d -安非他明（40 mg）和利地胺非他明（100 mg）以及安慰剂。反复评估安非他明的血浆浓度、主观效应和生命体征。采用室型模型确定药代动力学参数。结果：与d -安非他明组相比，利地安非他明组血浆浓度升高滞后时间为0.6±0.6 h（平均±SD），达到峰值时间为1.1±1.5 h，但两组最大浓度和总暴露量（AUC）无显著差异。与药代动力学一致，利德苯他明的主观和心血管兴奋作用也比d -安非他明晚。然而，与服用d -安非他明相比，服用利地安非他明后，与潜在滥用相关的主观药物效应（如药物喜好、药物兴奋、刺激、快乐、幸福和自信）的峰值评分没有差异。利地安非他明和d -安非他明也会产生相似的平均动脉血压、心率、体温、瞳孔大小和副作用的峰值升高。结论：利地安非他明与d -安非他明1h后给药的药代动力学和药效学相似。利地安非他明可能与d -安非他明有相似的口服滥用风险。该研究已在ClinicalTrials.gov注册（NCT02668926）。
Rationale: Lisdexamfetamine is a prodrug of D-amphetamine used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Lisdexamfetamine is thought to have a prolonged pharmacokinetic profile compared with oral D-amphetamine, possibly associated with lower drug liking and a lower risk of oral misuse. However, differences in the pharmacokinetics and pharmacodynamics of lisdexamfetamine and D-amphetamine have not been directly compared. Methods: Equimolar doses of D-amphetamine (40 mg) and lisdexamfetamine (100 mg), and placebo were administered in 24 healthy subjects in a randomized, double-blind, placebo-controlled, cross-over study. Plasma concentrations of amphetamine, subjective effects, and vital signs were repeatedly assessed. The pharmacokinetic parameters were determined using compartmental modeling. Results: The increase in plasma concentrations of amphetamine had a 0.6 ± 0.6 h (mean ± SD) longer lag time and reached peak levels 1.1 ± 1.5 h later after lisdexamfetamine administration compared with D-amphetamine administration, but no differences in maximal concentrations or total exposure (AUC) were found between the two treatments. Consistent with the pharmacokinetics, the subjective and cardiovascular stimulant effects of lisdexamfetamine also occurred later compared with D-amphetamine. However, no differences in peak ratings of potentially abuse-related subjective drug effects (e.g., drug liking, drug high, stimulation, happy, well-being, and self-confidence) were observed after lisdexamfetamine administration compared with D-amphetamine administration. Lisdexamfetamine and D-amphetamine also produced similar peak increases in mean arterial blood pressure, heart rate, body temperature, pupil size, and adverse effects. Conclusion: The pharmacokinetics and pharmacodynamics of lisdexamfetamine are similar to D-amphetamine administered 1h later. Lisdexamfetamine is likely associated with a similar risk of oral abuse as D-amphetamine. The study was registered at ClinicalTrials.gov (NCT02668926).
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影响因子：
10.6
作者：
ANGRIST, B;CORWIN, J;COOPER, T
通讯作者：
COOPER, T
影响因子：
3.7
作者：
Hysek CM;Simmler LD;Nicola VG;Vischer N;Donzelli M;Krähenbühl S;Grouzmann E;Huwyler J;Hoener MC;Liechti ME
通讯作者：
Liechti ME
DOI：
10.1017/s1461145713001132
发表时间：
2014-03-01
影响因子：
4.8
作者：
Hysek, Cedric M.;Simmler, Linda D.;Liechti, Matthias E.
通讯作者：
Liechti, Matthias E.
影响因子：
3.4
作者：
Kirkpatrick, Matthew G.;Gunderson, Erik W.;Hart, Carl L.
通讯作者：
Hart, Carl L.
影响因子：
6.4
作者：
Faraone, Stephen V.;Buitelaar, Jan
通讯作者：
Buitelaar, Jan