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.
