Licit & Illicit Opioids: Comparative Studies in Humans

描述（由申请人提供）：流行病学研究报告处方阿片类镇痛药的非医疗使用和转移增加。羟考酮以一系列配方上市，用于治疗急性和慢性疼痛。奥施康定(r)是一种缓释制剂，与立即释放产品相比，其销售剂量更高；由于意外成瘾、致命过量和犯罪转移的频率增加，这两种制剂都受到了大量负面宣传。氢可酮是一种相关的半合成阿片类药物，是美国最广泛使用的阿片类镇痛药，也是急诊室就诊中最常提到的处方阿片类药物。尽管它们在临床广泛使用，但很少有研究评估这些常用阿片类药物的滥用风险和临床药理学。该项目将采用受控的实验室程序来评估和表征羟考酮和氢可酮在一系列条件下对有阿片类药物滥用史的志愿者的影响。每项研究都将采用随机、安慰剂对照、双盲、主题内设计。为了安全起见，将在随机试验之前进行剂量上升试点评估。实验1将比较口服羟考酮和氢可酮与氢吗啡酮的作用，氢吗啡酮是一种已知具有高滥用潜力的泥类阿片激动剂，以及安慰剂在大剂量范围内的作用。实验2将重点关注奥施康定缓释产品，并将其在完整给药或经过篡改（粉碎以绕过缓释特征）与立即释放的羟考酮和安慰剂时的药代动力学和药效学特性进行比较；本研究的药代动力学分析将产生生物利用度数据。实验3将比较IVoxycodone和hydrocodone与吗啡、海洛因和安慰剂的药效学效果。在所有的研究中，数据将跨越多个领域收集。将分别收集生理和主观测量来评估安全性和滥用风险，并进行一系列精神运动和认知任务来评估这些药物的损害作用。这些研究将提供大量新知识，了解这些广泛使用的药物在治疗和超治疗剂量下在可能滥用它们的受试者群体中的相对滥用潜力和安全性。与公共卫生有关的信息将包括这些化合物的相对效力和耐受性、篡改已上市配方的后果，以及与这些制剂的安全性、计划和销售有关的经验信息。

DESCRIPTION (provided by applicant): Epidemiological studies report increasing non-medical use and diversion of prescription opioid analgesics. Oxycodone is marketed in an array of formulations and used for the treatment of acute and chronic pain. Oxycontin(r) is a sustained-release formulation which is marketed in higher dosage formulations compared to immediate release products; both formulations have received substantial negative publicity due to reports of increased frequency of unintentional addiction, fatal overdose and criminal diversion. Hydrocodone, a related semi-synthetic opioid, is the most widely prescribed opioid analgesic in the United States and the most frequently mentioned prescription opioid in emergency room admissions. Despite their widespread clinical use, few studies have evaluated the abuse liability and clinical pharmacology of these commonly used opioids. This project will employ controlled laboratory procedures to evaluate and characterize the effects of oxycodone and hydrocodone in volunteers with histories of opioid abuse under an array of conditions. Each of the studies will use randomized, placebo-controlled, double blind, within-subject designs. Dose rising pilot evaluations will precede randomized testing for safety purposes. Experiment 1 will compare the effects of oral oxycodone and hydrocodone to those of hydromorphone, a mud opioid agonist with known high abuse potential, and placebo over a broad range of doses. Experiment 2 will focus on the sustained-release Oxycontin(r) product and will compare its pharmacokinetic and pharmacodynamic properties when administered intact or after tampering (pulverizing to by-pass the sustained release features) to immediate release oxycodone and placebo; pharmacokinetic analyses will yield bioavailability data in this study. Experiment 3 will evaluate the pharmacodynamic effects of IVoxycodone and hydrocodone compared to morphine, heroin and placebo. In all studies, data will be collected across multiple domains. Physiological and subjective measures will be collected to assess safety and abuse liability, respectively, and a battery of psychomotor and cognitive tasks will assess the impairing effects of these agents. These studies will contribute substantial new knowledge about the relative abuse potential and safety of these widely available agents at therapeutic and supratherapeutic doses in a population of subjects who are likely to abuse them. Information relevant to the public health will include the relative potency and tolerability of these compounds, the consequences of tampering with marketed formulations, and empirical information relevant to safety, scheduling and marketing of these agents.