Department of Pharmacy Practice and Science, Maryland Poison Center, University of Maryland School of Pharmacy , Baltimore, MD , USA.
Clin Toxicol (Phila). 2015 Jun;53(5):477-85. doi: 10.3109/15563650.2015.1027903. Epub 2015 Apr 2.
Lisdexamfetamine is a pro-drug stimulant that requires the enzymatic hydrolysis of lysine from dexamphetamine for pharmacologic effects. There is limited information comparing non-therapeutic lisdexamfetamine and dextroamphetamine exposures.
The objective was to compare lisdexamfetamine exposures with dextroamphetamine/amphetamine extended release and dextroamphetamine/amphetamine immediate release.
A retrospective observational case series of single-substance exposures to lisdexamfetamine, dextroamphetamine/amphetamine extended release, or dextroamphetamine/amphetamine immediate release reported to the National Poison Data System from 2007 to 2012 was performed. Data were analyzed for demographics, reason, clinical effects, management site, and outcomes.
There were 23,553 exposures: lisdexamfetamine (7,113), dextroamphetamine/amphetamine extended release (6,245), and dextroamphetamine/amphetamine immediate release (10,195). The most frequent clinical effects observed for lisdexamfetamine, dextroamphetamine/amphetamine extended release, and dextroamphetamine/amphetamine immediate release were agitation (19.8%, 21.7%, and 25.1%, respectively) and tachycardia (19.2%, 22.8%, and 23.9%, respectively). The reason was most often exploratory (93.4%) in children < 6 years and therapeutic error (65.6%) in children aged 6-12 years. In adolescents and adults most common reasons were suicide attempts (28.4%) followed by abuse (19.5%) and therapeutic errors (18.8%). Overall, 61.6% of cases were managed in a health care facility, with the majority treated in the emergency department only. The majority of cases (76.0%) experienced no or minor effects. More serious outcomes (moderate/major/death) occurred in 21.2% of lisdexamfetamine, 24.7% of dextroamphetamine/amphetamine extended release, and 25.5% of dextroamphetamine/amphetamine immediate release. There were 4 deaths (1 dextroamphetamine/amphetamine extended release and 3 dextroamphetamine/amphetamine immediate release). In patients aged 6 years and more, abuse/misuse was more frequently reported for dextroamphetamine/amphetamine immediate release (32.5%) and dextroamphetamine/amphetamine extended release (23.0%) than that for lisdexamfetamine (13.5%). The odds of abuse/misuse was 2.3 (95% confidence interval [CI]: 2.0-2.4) times higher for dextroamphetamine/amphetamine immediate release than that for lisdexamfetamine and dextroamphetamine/amphetamine extended release combined; the odds of dextroamphetamine/amphetamine extended release abuse/misuse was 1.9 (95% CI: 1.7-2.2) times higher than lisdexamfetamine. In 2011, the number of lisdexamfetamine abuse/misuse cases exceeded dextroamphetamine/amphetamine extended release by approximately 26% and plateaued in 2012, but was significantly lower (∼75%) than dextroamphetamine/amphetamine immediate release.
Toxic effects were similar for all three drugs. Although the majority of cases were treated at health care facilities, the majority of patients experienced no effects or minor toxicity. Serious outcomes occurred in approximately 21% of lisdexamfetamine and 25% of dextroamphetamine/amphetamine extended release and dextroamphetamine/amphetamine immediate release. Lisdexamfetamine may have less abuse potential, especially compared with the immediate-release dextroamphetamine/amphetamine formulation.
Lisdexamfetamine 是一种前体药物兴奋剂，需要赖氨酸从右旋苯丙胺中酶解才能发挥药理作用。目前比较非治疗性 lisdexamfetamine 和右旋苯丙胺/苯丙胺释放的数据有限。
本研究旨在比较 lisdexamfetamine 与右旋苯丙胺/苯丙胺缓释和右旋苯丙胺/苯丙胺即时释放的暴露情况。
对 2007 年至 2012 年国家毒物数据系统报告的单一物质暴露于 lisdexamfetamine、右旋苯丙胺/苯丙胺缓释或右旋苯丙胺/苯丙胺即时释放的回顾性观察性病例系列进行了分析。对人口统计学、原因、临床效果、管理场所和结果进行了分析。
共报告了 23553 例暴露：lisdexamfetamine（7113）、右旋苯丙胺/苯丙胺缓释（6245）和右旋苯丙胺/苯丙胺即时释放（10195）。观察到最常见的临床效果是激动（19.8%、21.7%和 25.1%）和心动过速（19.2%、22.8%和 23.9%），对于 lisdexamfetamine、右旋苯丙胺/苯丙胺缓释和右旋苯丙胺/苯丙胺即时释放。原因主要是儿童<6 岁的探索性（93.4%）和儿童 6-12 岁的治疗错误（65.6%）。在青少年和成年人中，最常见的原因是自杀企图（28.4%），其次是滥用（19.5%）和治疗错误（18.8%）。总体而言，61.6%的病例在医疗机构接受治疗，其中大多数仅在急诊科治疗。大多数病例（76.0%）无或轻度影响。更严重的后果（中度/重度/死亡）发生在 lisdexamfetamine（21.2%）、右旋苯丙胺/苯丙胺缓释（24.7%）和右旋苯丙胺/苯丙胺即时释放（25.5%）。有 4 例死亡（1 例右旋苯丙胺/苯丙胺缓释和 3 例右旋苯丙胺/苯丙胺即时释放）。在 6 岁及以上的患者中，右旋苯丙胺/苯丙胺即时释放（32.5%）和右旋苯丙胺/苯丙胺缓释（23.0%）的滥用/误用较 lisdexamfetamine（13.5%）更为常见。右旋苯丙胺/苯丙胺即时释放的滥用/误用的几率是 lisdexamfetamine 的 2.3 倍（95%置信区间[CI]：2.0-2.4），右旋苯丙胺/苯丙胺缓释的滥用/误用几率是 lisdexamfetamine 的 1.9 倍（95%CI：1.7-2.2）。2011 年，lisdexamfetamine 滥用/误用病例数比右旋苯丙胺/苯丙胺缓释多约 26%，并在 2012 年达到平台期，但仍明显低于右旋苯丙胺/苯丙胺即时释放（约 75%）。
这三种药物的毒性作用相似。虽然大多数病例在医疗机构接受治疗，但大多数患者无影响或毒性较小。大约 21%的 lisdexamfetamine 和 25%的右旋苯丙胺/苯丙胺缓释和右旋苯丙胺/苯丙胺即时释放发生严重后果。与即时释放的右旋苯丙胺/苯丙胺制剂相比，lisdexamfetamine 的滥用潜力可能较小。
