Pharmacokinetic and pharmacodynamic analysis of d-amphetamine in an attention task in rodents.
Pharmacokinetic and pharmacodynamic analysis of d-amphetamine in an attention task in rodents.
复制标题
d-苯丙胺在啮齿动物注意任务中的药代动力学和药效学分析。
DOI：
10.1097/fbp.0000000000000409
复制
发表时间：
2018
影响因子：
1.6
通讯作者：
Katz,JonathanL
中科院分区：
文献类型：
--
作者：
Slezak,JonathanM;Mueller,Melanie;Ricaurte,GeorgeA;Katz,JonathanL
安非他明是一种常见的治疗药物，可缓解儿童和成人注意力缺陷多动障碍 (ADHD) 相关的核心症状。目前的研究使用注意力转化模型，即大鼠的五选择串行反应时间（5-CSRT）程序，来检查 d-苯丙胺的时程效应。不同剂量的 d-苯丙胺的作用与药物血浆浓度有关，这是在临床研究中采用的综合药代动力学/药效学评估后形成的。我们试图确定提高 5-CSRT 手术表现的急性药物血浆浓度是否与对诊断为 ADHD 的患者具有治疗作用的浓度相似。药代动力学/药效学评估结果表明，与 5-CSRT 程序性能改善相关的 d-苯丙胺血浆浓度与临床试验中报道的治疗效果重叠。目前的研究结果表明，5-CSRT 程序可能是一个有用的临床前模型，用于预测新型 ADHD 疗法的效用及其有效浓度。
Amphetamine is a common therapeutic agent for alleviating the core symptoms associated with attention-deficit hyperactivity disorder (ADHD) in children and adults. The current study used a translational model of attention, the five-choice serial reaction time (5-CSRT) procedure with rats, to examine the time-course effects of d-amphetamine. Effects of different dosages of d-amphetamine were related to drug–plasma concentrations, fashioned after comprehensive pharmacokinetic/pharmacodynamic assessments that have been employed in clinical investigations. We sought to determine whether acute drug–plasma concentrations that enhance performance in the 5-CSRT procedure are similar to those found to be therapeutic in patients diagnosed with ADHD. Results from the pharmacokinetic/pharmacodynamic assessment indicate that d-amphetamine plasma concentrations associated with improved performance on the 5-CSRT procedure overlap with those that have been reported to be therapeutic in clinical trials. The current findings suggest that the 5-CSRT procedure may be a useful preclinical model for predicting the utility of novel ADHD therapeutics and their effective concentrations.