Jasinski D R, Krishnan S
Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA.
J Psychopharmacol. 2009 Jun;23(4):410-8. doi: 10.1177/0269881108093841. Epub 2008 Jul 17.
The objective of this study is to determine the safety, tolerability and abuse liability of single intravenous (i.v.) doses of lisdexamfetamine dimesylate (LDX) and immediate-release d-amphetamine sulphate in adult stimulant abusers compared with placebo. Adult substance abusers were enrolled in this phase I, randomized, single-centre, double-blind study. An initial cohort of three subjects was enrolled to assess safety followed by a primary cohort that consisted of nine subjects. Single i.v. doses of LDX (25 or 50 mg), immediate-release d-amphetamine sulphate (10 or 20 mg) or placebo were administered at a minimum of 48-h intervals in a single-dose, three-way crossover design. 20 mg of d-amphetamine showed significantly increased abuse-related liking scores compared with placebo (P < 0.05), whereas the liking effects of 50 mg LDX did not significantly differ from placebo. The mean C(max) of d-amphetamine was 38.9 +/- 8.1 and 105 +/- 91.4 ng/ml after the administration of 50 mg LDX and 20 mg d-amphetamine respectively. The mean T(max) of d-amphetamine was 2.51 h after the administration of 50 mg LDX and 0.82 h after the administration of 20 mg d-amphetamine. LDX was well tolerated in this population. In contrast to d-amphetamine, LDX administered intravenously did not produce significant subjective abuse-related liking scores at assessed doses.
本研究的目的是确定与安慰剂相比，单次静脉注射（i.v.）不同剂量的二甲磺酸赖右苯丙胺（LDX）和速释硫酸右旋苯丙胺在成年兴奋剂滥用者中的安全性、耐受性和滥用倾向。成年药物滥用者参与了这项单中心、随机、双盲的I期研究。最初招募了3名受试者评估安全性，随后的主要队列由9名受试者组成。采用单剂量、三交叉设计，以至少48小时的间隔单次静脉注射LDX（25或50mg）、速释硫酸右旋苯丙胺（10或20mg）或安慰剂。与安慰剂相比，20mg的右旋苯丙胺显示出与滥用相关的喜好评分显著增加（P<0.05），而50mg LDX的喜好效应与安慰剂无显著差异。分别给予50mg LDX和20mg右旋苯丙胺后，右旋苯丙胺的平均C(max)分别为38.9±8.1和105±91.4ng/ml。给予50mg LDX后，右旋苯丙胺的平均T(max)为2.51小时，给予20mg右旋苯丙胺后为0.82小时。该人群对LDX耐受性良好。与右旋苯丙胺不同，静脉注射LDX在评估剂量下未产生显著的与主观滥用相关的喜好评分。
