CANCER PAIN: PHARMACOKINETIC CORRELATES OF ANALGESIA

本提案的总体目标是建立药理学基础 麻醉性镇痛药在癌症治疗中的合理使用 成人和儿童的疼痛。 拟议的研究旨在确定 药代动力学因素与药理作用之间的关系 对于包括吗啡在内的一系列常用麻醉性镇痛药， 美沙酮、哌替啶、左啡诺、氢吗啡酮和丁丙诺啡。 这些 药物将通过口服和静脉途径给药， 以单剂量和重复给药方案施用。 数据 生物利用度、吸收率、消除率和其他药代动力学 从血浆、唾液和脑脊液采样中挑选的参数 结合同时进行的临床镇痛评估， 开发适当药物给药方案的必要信息， 在癌症治疗中最大限度地镇痛并最大限度地减少副作用 痛苦 新给药途径的具体研究，包括 将进行硬膜外和蛛网膜下腔途径，以评估 这些方法的相对有用性， 药代动力学-药理学相关性。 该提案还涉及 通过开发一种用于测量儿童疼痛和镇痛的 测量儿童疼痛的方法，然后可以应用于 麻醉性镇痛药在麻醉性疾病中的效力和相对效力的评估 儿童疼痛的管理。

The overall objective of this proposal is to develop a pharmacologic basis for the rationale use of narcotic analgesics in the managements of cancer pain in adults and children. The studies proposed are designed to define the relationship between pharmacokinetic factors and pharmacologic effects for a series of commonly used narcotic analgesics including morphine, methadone, meperidine, levorphanol, hydromorphone and buprenorphine. These drugs will be administered by both the oral and intravenous routes of administration in single dose and repetitive dosing schedules. Data on the bioavailability, rates of absorption, elimination and other pharmacokinetic parameters culled from plasma, saliva and cerebrospinal fluid sampling coupled with concurrent clinical analgesic assessments will provide the necessary information to develop appropriate drug dosing regimens to maximize analgesia and minimize side effects in the management of cancer pain. Specific studies of novel routes of drug administration including the epidural and subarachnoid routes will aso be carried out to assess the relative usefulness of these approaches and the pharmacokinetic-pharmacologic correlates. This proposal also addresses the problem of measuring pain and analgesia in children by developing a methodology to measure pain in children which can then be applied to the assessment of the efficacy and relative potency of narcotic analgesics in the management of pain in children.