Dihydroetorphine for the provision of pain relief and anaesthesia

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 peak respiratory depression in said subject is 20 to 80% relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of providing analgesia 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 resulting ventilation ratio in said subject is at least 0.3.

A method as claimed in any one of claims 40 to 442, wherein the resulting ventilation ratio in said subject is between 0.3 and 0.6.

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 ED75 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

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 ED50 dose and less than the ED75 dose and the level of respiratory depression in said subject is 50% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

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 ED75 dose and less than the ED95 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

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.

A method of providing pain relief in a human subject in need thereof whilst minimising risk of apnoea comprising administering a dose of (R)-dihydroetorphine that provides dose dependent pain relief and dose-independent respiratory depression.

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 EMIN in ventilation of 30-50% relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of treating pain in a human subject comprising administering to said subject an effective dose of (R)-dihydroetorphine, wherein during said treating at least one opioid-related side effect is reduced compared to treatment with an equianalgesic dose of fentanyl.

A method as claimed in any preceding claim, wherein the dose of (R)-dihydroetorphine is administered intravenously.

A method as claimed in any preceding claim, wherein the pain treated is nociceptive pain.

A method of providing anaesthesia 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 0.15 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.

A method of providing anaesthesia 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 0.15 mg/kg and the peak respiratory depression in said subject is 20 to 80% relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of providing anaesthesia 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 0.15 μg/kg and the resulting ventilation ratio in said subject is at least 0.3.

A method of providing anaesthesia 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 ED75 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of providing anaesthesia 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 ED50 dose and less than the ED75 dose and the level of respiratory depression in said subject is 50% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of providing anaesthesia 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 ED75 dose and less than the ED95 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of providing anaesthesia 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 1.5 times and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of providing anaesthesia in a human subject in need thereof whilst minimising risk of apnoea comprising administering a dose of (R)-dihydroetorphine that provides dose dependent pain relief and dose-independent respiratory depression.

A method of providing maximum anaesthesia in a human subject in need thereof whilst minimising risk of apnoea comprising administering a dose of (R)-dihydroetorphine which causes a EMIN in ventilation of 30-50% relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method as claimed in claim 292 or 293, wherein said (R)-dihydroetorphine is administered in a dose of 0.2 to 0.3 μg/kg.

A method of providing anaesthesia in a human subject comprising administering to said subject an effective dose of (R)-dihydroetorphine, wherein during said treating at least one opioid-related side effect is reduced compared to treatment with an equianalgesic dose of fentanyl.

A method as claimed in any preceding claim, wherein the dose of (R)-dihydroetorphine is administered intravenously.

A method as claimed in any preceding claim, wherein the pain treated is nociceptive pain.

(R)-dihydroetorphine for the treatment of pain, wherein during said treatment 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.

(R)-dihydroetorphine for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of at least 0.01 μg/kg, preferably at least 0.05 μg/kg, and the peak respiratory depression in said subject is 20 to 80% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of at least 0.01 μg/kg, preferably at least 0.05 μg/kg, and the ventilation ratio in said subject is at least 0.3.

(R)-dihydroetorphine for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED75 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED50 dose and less than the ED75 dose and the level of respiratory depression in said subject is 50% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED75 dose and less than the ED95 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for the treatment of pain, wherein during said treatment 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.

(R)-dihydroetorphine for the treatment of pain whilst minimising risk of apnoea, wherein during said treatment a dose of (R)-dihydroetorphine that provides dose dependent pain relief and dose-independent respiratory depression is administered.

(R)-dihydroetorphine for the treatment of pain whilst minimising risk of apnoea wherein during said treatment a dose of (R)-dihydroetorphine which causes a EMIN in ventilation of 30-50% relative to the baseline level pre-administration of (R)-dihydroetorphine is administered.

(R)-dihydroetorphine for the treatment of pain, wherein during said treatment at least one opioid-related side effect is reduced compared to treatment with an equianalgesic dose of fentanyl.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment 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.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during treatment said (R)-dihydroetorphine is administered in a dose of at least 0.01 μg/kg, preferably at least 0.05 μg/kg, and the peak respiratory depression in said subject is 20 to 80% relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of at least 0.01 μg/kg, preferably at least 0.05 μg/kg, and the ventilation ratio in said subject is at least 0.3.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED75 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED50 dose and less than the ED75 dose and the level of respiratory depression in said subject is 50% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED75 dose and less than the ED95 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment 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.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment a dose of (R)-dihydroetorphine that provides dose dependent pain relief and dose-independent respiratory depression is administered.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment a dose of (R)-dihydroetorphine which causes a EMIN in ventilation of 30-50% relative to the baseline level pre-administration of (R)-dihydroetorphine is administered.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain, wherein during said treatment at least one opioid-related side effect is reduced compared to treatment with an equianalgesic dose of fentanyl.

(R)-dihydroetorphine for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of at least 0.15 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.

(R)-dihydroetorphine for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of at least 0.15 μg/kg and the peak respiratory depression in said subject is 20 to 80% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of at least 0.15 μg/kg and the ventilation ratio in said subject is at least 0.3.

(R)-dihydroetorphine for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED75 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED50 dose and less than the ED75 dose and the level of respiratory depression in said subject is 50% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED75 dose and less than the ED95 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for providing anaesthesia, wherein during said treatment 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 1.5 times and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for providing anaesthesia whilst minimising risk of apnoea, wherein during said treatment a dose of (R)-dihydroetorphine that provides dose dependent pain relief and dose-independent respiratory depression is administered.

(R)-dihydroetorphine for providing anaesthesia whilst minimising risk of apnoea, wherein during said treatment a dose of (R)-dihydroetorphine which causes a EMIN in ventilation of 30-50% relative to the baseline level pre-administration of (R)-dihydroetorphine is administered.

(R)-dihydroetorphine for providing anaesthesia, wherein during said treatment at least one opioid-related side effect is reduced compared to treatment with an equianalgesic dose of fentanyl.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of at least 0.15 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.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during treatment said (R)-dihydroetorphine is administered in a dose of at least 0.15 μg/kg and the peak respiratory depression in said subject is 20 to 80% relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of at least 0.15 μg/kg and the ventilation ratio in said subject is at least 0.3.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED75 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED50 dose and less than the ED75 dose and the level of respiratory depression in said subject is 50% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose greater than the ED75 dose and less than the ED95 dose and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia n, wherein during said treatment 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 1.5 times and the level of respiratory depression in said subject is 65% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during said treatment a dose of (R)-dihydroetorphine that provides dose dependent pain relief and dose-independent respiratory depression is administered.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during said treatment a dose of (R)-dihydroetorphine which causes a EMIN in ventilation of 30-50% relative to the baseline level pre-administration of (R)-dihydroetorphine is administered.

Use of (R)-dihydroetorphine in the manufacture of a medicament for providing anaesthesia, wherein during said treatment at least one opioid-related side effect is reduced compared to treatment with an equianalgesic dose of fentanyl.

A method of providing pain relief or anaesthesia in a human subject in need thereof comprising administering (R)-dihydroetorphine to said subject, wherein said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the level of respiratory depression in said subject is 85 or less % relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of providing pain relief or anaesthesia in a human subject in need thereof comprising administering (R)-dihydroetorphine to said subject, wherein said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the peak respiratory depression in said subject is 15 to 80% relative to the baseline level pre-administration of (R)-dihydroetorphine.

A method of providing pain relief or anaesthesia in a human subject in need thereof comprising administering (R)-dihydroetorphine to said subject, wherein said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the resulting ventilation ratio in said subject is at least 0.15.

(R)-dihydroetorphine for providing pain relief or anaesthesia, wherein said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the level of respiratory depression in the subject is 85% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for providing pain relief or anaesthesia, wherein said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the peak respiratory depression in the subject is 15 to 80% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

(R)-dihydroetorphine for providing pain relief or anaesthesia, wherein said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the ventilation ratio in the subject is at least 0.15.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain or anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the level of respiratory depression in said subject is 85% or less relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain or anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the peak respiratory depression in said subject is 15 to 80% relative to the baseline level pre-administration of (R)-dihydroetorphine.

Use of (R)-dihydroetorphine in the manufacture of a medicament for the treatment of pain or anaesthesia, wherein during said treatment said (R)-dihydroetorphine is administered in a dose of 0.20 to 0.5 μg/kg and the ventilation ratio in said subject is at least 0.3.