CANCER PAIN--PHARMACOKINETIC CORRELATES OF ANALGESIA

这项建议的主要目的是为了更好地了解 阿片类药物临床药理学的理论和实践 人类的止痛药 这些知识将有助于发展 有科学依据的使用这些药物治疗疼痛的指南 管理 我们已经开发了用于评估疼痛的镇痛测定方法 和阿片类药物副作用，具体和敏感的分析方法， 定量生物流体中的阿片样物质及其代谢物以及 将药物浓度与阿片样物质作用相关的PK-PD分析。 我们将 现在扩展这种方法，并应用PK-PD分析来阐明 吗啡药理学，改进常用的给药方式（如口服） 新的（透皮）阿片类药物治疗和耐受性研究 和交叉耐受性。 我们还计划研究稳态 吗啡及其代谢物在儿童中的浓度以及 成人肝肾功能不全及不良反应。 这些信息将提供定量数据来证实或反驳 临床给药指南，并将提供有关 药物处置的年龄。

The major objectives of this proposal are to better understand the theoretical and practical aspects of the clinical pharmacology of opioid analgesics in humans. This knowledge will facilitate the development of scientifically based guidelines for the use of these drugs in pain management. We have developed analgesic assay methods for assessing pain and opioid side effects, specific and sensitive analytical methods to quantitate opioids and their metabolites in biofluids and techniques of PK-PD analysis that relate drug concentration to opioid effects. We will now extend this approach and apply PK-PD analysis to the elucidation of morphine pharmacology, the improved administration of common (e.g. oral) and novel (transdermal) opioid therapies and investigation of tolerance and cross-tolerance. We also plan to study the steady-state concentrations of morphine and its metabolites in children as well as adults with hepatic and renal dysfunction as well as adverse effects. This information will provide quantitative data to substantiate or refute clinical dosing guidelines and will provide information about effect of age on drug disposition.