Control of severe pain during palliative care in cancer patients can be a vexing problem, particularly when opioid tolerance has emerged. The risk of cardio-respiratory depression is relatively high with opioid drugs. Patients receiving Ketamine are far less susceptible to cardio-respiratory depression than patients receiving opioids. Continuous Ketamine infusion is a useful treatment under these conditions, however, it requires continuous intravenous access, infusion pumps and a general escalation of care, including hospital admission with administration and monitoring in acute or intensive care units and its associated costs. Although long acting, slow release oral and transdermal opioids are available and can often substitute for continuous opioid infusions, more desirable slow release and long-acting (12 to 48 hr) Ketamine formulations are not available. Subcutaneous, intravenous or intramuscular long-acting Ketamine formulations could greatly reduce the number of administrations as well as the risks of cardio-respiratory depression. It would enable its administration for severe pain in hospital, but also in hospice and even home settings, allowing for a reduction instead of an intensification of care. Since psychomimetic reactions can follow Ketamine administration, it is standard practice to co-administer a benzodiazepine such as Lorazepam to offset possible undesirable side effects of Ketamine.
We hope to obtain funding to develop a dendrimer-based Ketamine-Lorazepam therapeutic that provides analgesia and sedation for 12-48 hours following a single administration either by subcutaneous, intramuscular or intravenous route. Ketamine and Lorazepam should be slowly released from the dendrimer by means of a controlled mechanism to reach appropriate dose levels over time for improved, lower risk, end-of-life palliative care in cancer patients.
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