Opioid delivery system

• US 7,648,981 B2
• Filed: 03/01/2004
• Issued: 01/19/2010
• Est. Priority Date: 02/28/2003
• Status: Expired due to Fees

• Current Assignee: YM BioSciences Inc. (Gilead Sciences Inc.)
• Original Assignee: YM BioSciences Inc. (Gilead Sciences Inc.)
• Inventors: Pliura, Diana Helen, Hung, Orlando Ricardo, Shafer, Steven Louis
• Primary Examiner(s): Arnold; Ernst V
• Assistant Examiner(s): ALSTRUM ACEVEDO, JAMES HENRY
• Application Number:
  US10/788,466
• Publication Number:
  US 20040228808A1
• Time in Patent Office: 2,150 Days
• Field of Search: 424/43, 424/45, 424/417, 424/450
• US Class Current: 514/225.5
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

An opioid formulation for pulmonary administration in the treatment or management of pain, a pulmonary drug delivery device containing, method of administering, kit containing, and uses of same. The formulation contains at least one rapid-onset opioid and preferably also contains a sustained-effect opioid to reduce the frequency of administration. The invention employs the side effects of the opioid formulation to permit patients to self-limit drug intake, thereby avoiding toxicity while achieving analgesia. A pharmacokinetic and pharmacodynamic model is employed to determine optimum drug formulations and optimum parameters for administration.

Claims

1. A pain management method enabling a pain sufferer to self-medicate by repeated dosing with an opioid formulation to achieve analgesia while avoiding toxicity, wherein the method relies solely on the actions of the pain sufferer to manage intake of said opioid during the medication process, said method comprising the steps of:

the pain sufferer continuously inhaling the formulation using a pulmonary drug delivery device to produce analgesia; and

stopping inhalation during the medication process when satisfactory analgesia is achieved or at the onset of a side effect;

wherein the formulation comprises fentanyl and liposomally encapsulated fentanyl;

the concentration of said fentanyl and liposomally encapsulated fentanyl, and amount of and particle size of the formulation delivered from the device on each inhalation, being selected so that, during inhalation, analgesia is achieved before the onset of said side effect, and the onset of said side effect occurs before the onset of toxicity, and so that the maximum total opioid plasma concentration does not reach toxic levels, whereby the onset of said side effect can be used by the pain sufferer to terminate inhalation to avoid toxicity, wherein the ratio of said fentanyl to liposomally encapsulated fentanyl is selected such that a combined pharmacokinetic profile of the fentanyl and the liposomally encapsulated fentanyl has a combined effect curve providing a peak concentration at an effect site at between 10 and 30 minutes and a concentration at the effect site of a magnitude of at least 85% of said peak concentration for at least 2 hours.

2. The method of claim 1 wherein the pulmonary drug delivery device is adapted to dispense the formulation only through an exercise of conscious effort by the patient.

3. A pulmonary drug delivery device for use in the pain management method of claim 2, comprising:

a container containing a formulation comprising an effective amount of fentanyl and liposomally encapsulated fentanyl;

wherein the device is adapted to dispense the formulation only through an exercise of conscious effort by the patient; and

the concentration of said fentanyl and liposomally encapsulated fentanyl, and amount of and particle size of the formulation delivered from the device on each inhalation, is selected so that, during inhalation, analgesia is achieved before the onset of said side effect, and the onset of said side effect occurs before the onset of toxicity, and so that the maximum total opioid plasma concentration does not reach toxic levels, whereby the onset of said side effect can be used by the patient to terminate inhalation to avoid toxicity, wherein the ratio of said fentanyl to liposomally encapsulated fentanyl is selected such that a combined pharmacokinetic profile of the fentanyl and the liposomally encapsulated fentanyl has a combined effect curve providing a peak concentration at an effect site at between 10 and 30 minutes and a concentration at the effect site of a magnitude of at least 85% of said peak concentration for at least 2 hours.

4. The device of claim 3 wherein said device has a weight ranging from 250 to 2500 grams.

5. The device of claim 3 further comprising an outlet through which the formulation is dispensed, wherein said outlet comprises a fenestration which must be sealed by the lips of the patient in order for the formulation to be dispensed.

6. The device of claim 3 wherein the dispensing of the formulation is breath actuated.