Pulmonary delivery of opioids as pain therapeutics.

Pulmonary opioid delivery, on the basis of the fact that small molecular entities can be rapidly and completely absorbed from the peripheral lung, poses a unique opportunity for the treatment of severe (breakthrough) pain, which currently is treated with intravenous therapy. Early clinical studies involving inhaled opioids were focused on treatment of dyspnoea and not pain management, but they showed that inhalation of various opioid compounds is safe, even in severely ill patients. The advent of specialized and efficient pulmonary drug delivery systems has facilitated the evaluation of inhaled opioids, such as morphine and fentanyl, for management of severe pain associated with surgery or malignant disease. This review will summarize recent literature on the pharmacokinetics and pharmacodynamics of inhaled opioids and will discuss safety and efficacy in comparison to injection and other opioid dosage forms available for pain therapy. Finally, regulatory considerations will be discussed towards the approval of this new delivery paradigm for opioid drugs.