Dihydroetorphine for the provision of pain relief and anaesthesia

Abstract

The present invention provides a method of providing pain relief in a human subject in need thereof comprising administering (R)-dihydroetorphine to said subject, wherein said (R)-dihydroetorphine is administered in a dose of at least 0.01 μg/kg, preferably at least 0.05 μg/kg, and the level of respiratory depression in said subject is 65 or less % relative to the baseline level pre-administration of (R)-dihydroetorphine.

1 - 400 . (canceled) 
     
     
         401 . A method of providing pain relief to a human subject in need thereof comprising administering (R)-dihydroetorphine to said subject, wherein said (R)-dihydroetorphine is administered in a dose that increases the pain threshold value relative to the baseline level pre-administration of (R)-dihydroetorphine by at least 1.2 times and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine. 
     
     
         402 . The method as claimed in  claim 401 , wherein said method increases the pain threshold level in said subject relative to the baseline level pre-administration of (R)-dihydroetorphine by at least 1.5 times. 
     
     
         403 . The method as claimed in  claim 401 , wherein said method increases the pain threshold level in said subject relative to the baseline level pre-administration of (R)-dihydroetorphine by 1.2 to 3.0 times. 
     
     
         404 . The method as claimed in  claim 401 , wherein said pain threshold levels are measured by applying pain using a transcutaneous electrical stimulus to the skin over the tibial bone and increasing the electrical stimulus at a rate of 0.5 mA per 2 s. 
     
     
         405 . The method as claimed in  claim 401 , wherein the level of respiratory depression in said subject is between 40 and 65% relative to the baseline level pre-administration of (R)-dihydroetorphine. 
     
     
         406 . The method as claimed in  claim 401 , wherein said respiratory depression is the average respiratory depression measured under iso-hypercapnic conditions for 1 hour following administration of said (R)-dihydroetorphine intravenously over 10 minutes. 
     
     
         407 . The method as claimed in  claim 401 , wherein said respiratory depression is the average respiratory depression measured under iso-hypercapnic conditions for 1 hour with end tidal oxygen level clamped at 110 mmHg and end tidal carbon dioxide clamped at a level causing ventilation levels of 20±2 L/min. 
     
     
         408 . The method as claimed in  claim 407 , wherein said end tidal carbon dioxide level is clamped at 50 mmHg. 
     
     
         409 . The method as claimed in  claim 401 , wherein during said method one or more opioid-related effects selected from dizziness, euphoria, nausea, sedation and dysphoria are minimised. 
     
     
         410 . The method as claimed in  claim 401 , wherein said opioid-related side effect is reduced compared to treatment with an equianalgesic dose of fentanyl. 
     
     
         411 . The method as claimed in  claim 401 , wherein
 the average NAS score for dizziness is less than 50 in the 7.5 hours post administration of (R)-dihydroetorphine; and/or   the average NAS score for euphoria is less than 60 in the 7.5 hours post administration of (R)-dihydroetorphine; and/or   the average NAS score for nausea is less than 40 in the 7.5 hours post administration of (R)-dihydroetorphine; and/or   the average NAS score for sedation is less than 60 in the 7.5 hours post administration of (R)-dihydroetorphine; and/or   the average NAS score for dysphoria is less than 40 in the 7.5 hours post administration of (R)-dihydroetorphine.   
     
     
         412 . A method of providing pain relief in a human subject in need thereof comprising administering (R)-dihydroetorphine to said subject, wherein said (R)-dihydroetorphine is administered in a dose greater than the ED 75  dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine. 
     
     
         413 . The method as claimed in  claim 412 , wherein (R)-dihydroetorphine is administered in a dose greater than the ED 85  dose. 
     
     
         414 . The method as claimed in  claim 412 , wherein (R)-dihydroetorphine is administered in a dose greater than the ED 90  dose. 
     
     
         415 . The method as claimed in  claim 412 , wherein (R)-dihydroetorphine is administered in a dose between the ED 75  dose and the ED 95  dose. 
     
     
         416 . A method of providing pain relief in a human subject in need thereof comprising administering (R)-dihydroetorphine to said subject, wherein said (R)-dihydroetorphine is administered in a dose greater than the ED 50  dose and less than the ED 75  dose and the level of respiratory depression in said subject is 50% or less relative to the baseline level pre-administration of (R)-dihydroetorphine. 
     
     
         417 . A method of providing maximum pain relief in a human subject in need thereof whilst minimising risk of apnoea comprising administering a dose of (R)-dihydroetorphine which causes a E MIN  in ventilation of 30-50% relative to the baseline level pre-administration of (R)-dihydroetorphine. 
     
     
         418 . The method as claimed in  claim 401 , wherein the dose of (R)-dihydroetorphine is administered intravenously. 
     
     
         419 . The method as claimed in  claim 401 , wherein the pain treated is nociceptive pain.