Licit & Illicit Opioids: Comparative Studies in Humans

描述(由申请人提供)：流行病学研究报告称，处方阿片类镇痛剂的非医疗用途和转用增加。羟考酮以一系列配方销售，用于治疗急性和慢性疼痛。OxyContin(R)是一种缓释制剂，与速释产品相比，它以更高剂量的制剂上市；由于有报道称，意外上瘾、致命过量和犯罪转移的频率增加，这两种制剂都受到了相当大的负面宣传。氢可酮是一种相关的半合成阿片类药物，是美国处方最广泛的阿片类止痛药，也是急诊室入院时提到最多的处方阿片类药物。尽管它们在临床上广泛使用，但很少有研究评估这些常用阿片类药物的滥用易感性和临床药理学。该项目将采用受控实验室程序来评估羟考酮和氢可酮在一系列条件下有阿片类药物滥用史的志愿者身上的效果。每项研究都将使用随机、安慰剂对照、双盲、受试者内设计。出于安全目的，剂量增加试点评估将在随机测试之前进行。实验1将比较口服羟考酮和氢可酮与氢吗啡酮的效果，氢吗啡酮是一种已知具有很高滥用潜力的泥阿片激动剂，而安慰剂则在广泛的剂量范围内。实验2将重点放在缓释Oxycontin(R)产品上，并将比较其在完整或篡改(粉碎以绕过缓释功能)与立即释放羟考酮和安慰剂时的药代动力学和药效学特性；药代动力学分析将在本研究中产生生物利用度数据。实验3将评估丙氧可酮和氢可酮与吗啡、海洛因和安慰剂的药效学效果。在所有研究中，将跨多个领域收集数据。将收集生理和主观指标，分别评估安全和滥用风险，一系列精神运动和认知任务将评估这些制剂的损害影响。这些研究将对这些广泛使用的制剂在治疗和超治疗剂量下在可能滥用它们的受试者中的相对滥用潜力和安全性提供实质性的新知识。与公众健康相关的信息将包括这些化合物的相对效力和耐受性，篡改上市配方的后果，以及与这些制剂的安全性、时间表和营销相关的经验信息。

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.