Method of providing sustained analgesia with buprenorphine
OwnerRobert F. Reder, Paul D. Goldenheim +1inventors
InventorsRobert F. Reder, Paul D. Goldenheim, Robert F. Kaiko
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Abstract
A method of effectively treating pain in humans is achieved by administering buprenorphine in accordance with first order kinetics over an initial three-day dosing interval, such that a maximum plasma concentration from about 20 pg/ml to about 1052 pg/ml is attained, and thereafter maintaining the administration of buprenorphine for at least an additional two-day dosing interval in accordance with substantially zero order kinetics, such that the patients experience analgesia throughout the at least two-day additional dosing interval.
Claims68
A method of effectively treating pain in humans, comprising
- administering buprenorphine to human patients in a maimer such that the following mean plasma concentrations are achieved over a 72 hour dosing interval:
- a mean plasma concentration from about 0.3 to about 113 pg/ml at about 6 hours after initiation of the dosing interval;
- a mean plasma concentration from about 3 to about 296 pg/ml at about 12 hours after initiation of the dosing interval;
- a mean plasma concentration from about 7 to about 644 pg/ml at about 24 hours after initiation of the dosing interval;
- a mean plasma concentration from about 13 to about 753 pg/ml at about 36 hours after initiation of the dosing interval;
- a mean plasma concentration from about 16 to about 984 pg/ml at about 48 hours after initiation of the dosing interval;
- a mean plasma concentration from about 20 to about 984 pg/ml at about 60 hours after initiation of the dosing interval;
- a mean plasma concentration from about 21 to about 1052 pg/ml at about 72 hours after initiation of the dosing interval;
- and
- thereafter administering the buprenorphine in a manner such that the mean plasma concentrations are maintained from about 19 to about 1052 pg/ml over at least the next 48 hours.
The method of claim 5, wherein said administration is accomplished by applying a transdermal delivery system to the skin of a patient, and maintaining said transdermal delivery system in contact with the patient's skin for at least 5 days.
A method of effectively treating pain in humans, comprising
- administering buprenorphine to human patients in a manner such that the following mean plasma concentrations are achieved over a 72 hour dosing interval:
- a mean plasma concentration from about 1 to about 28 pg/ml at about 6 hours after initiation of the dosing interval;
- a mean plasma concentration from about 14 to about 74 pg/ml at about 12 hours after initiation of the dosing interval;
- a mean plasma concentration from about 30 to about 161 pg/ml at about 24 hours after initiation of the dosing interval;
- a mean plasma concentration from about 51 to about 188 pg/ml at about 36 hours after initiation of the dosing interval;
- a mean plasma concentration from about 62 to about 246 pg/ml at about 48 hours after initiation of the dosing interval;
- a mean plasma concentration from about 79 to about 246 pg/ml at about 60 hours after initiation of the dosing interval;
- a mean plasma concentration from about 85 to about 263 pg/ml at about 72 hours after initiation of the dosing interval;
- and
- thereafter administering the buprenorphine in a manner such that the mean plasma concentrations are maintained from about 77 to about 263 pg/ml over at least the next 48 hours.
A method of effectively treating pain in humans, comprising
- administering buprenorphine to human patients in a manner such that the following mean plasma concentrations are achieved over a 72 hour dosing interval:
- a mean plasma concentration from about 0.3 to about 7 pg/ml at about 6 hours after initiation of the dosing interval;
- a mean plasma concentration from about 4 to about 19 pg/ml at about 12 hours after initiation of the dosing interval;
- a mean plasma concentration from about 7 to about 40 pg/ml at about 24 hours after initiation of the dosing interval;
- a mean plasma concentration from about 13 to about 47 pg/ml at about 36 hours after initiation of the dosing interval;
- a mean plasma concentration from about 16 to about 62 pg/ml at about 48 hours after initiation of the dosing interval;
- a mean plasma concentration from about 20 to about 62 pg/ml at about 60 hours after initiation of the dosing interval;
- a mean plasma concentration from about 21 to about 66 pg/ml at about 72 hours after initiation of the dosing interval;
- and
- thereafter administering the buprenorphine in a manner such that the mean plasma concentrations are maintained from about 19 to about 66 pg/ml over at least the next 48 hours.
A method of effectively treating pain in humans, comprising
- administering buprenorphine to human patients in a manner such that the following mean plasma concentrations are achieved over a 72 hour dosing interval:
- a mean plasma concentration from about 0.7 to about 14 pg/ml at about 6 hours after initiation of the dosing interval;
- a mean plasma concentration from about 7 to about 37 pg/ml at about 12 hours after initiation of the dosing interval;
- a mean plasma concentration from about 15 to about 80 pg/ml at about 24 hours after initiation of the dosing interval;
- a mean plasma concentration from about 25 to about 94 pg/ml at about 36 hours after initiation of the dosing interval;
- a mean plasma concentration from about 31 to about 123 pg/ml at about 48 hours after initiation of the dosing interval;
- a mean plasma concentration from about 40 to about 123 pg/ml at about 60 hours after initiation of the dosing interval;
- a mean plasma concentration from about 42 to about 132 pg/ml at about 72 hours after initiation of the dosing interval;
- and
- thereafter administering the buprenorphine in a manner such that the mean plasma concentrations are maintained from about 38 to about 132 pg/ml over at least the next 48 hours.
A method of effectively treating pain in humans, comprising administering buprenorphine to human patients in a manner such that the following mean plasma concentrations are achieved over a 72 hour dosing interval:
- a mean plasma concentration from about 3 to about 57 pg/ml at about 6 hours after initiation of the dosing interval;
- a mean plasma concentration from about 28 to about 148 pg/ml at about 12 hours after initiation of the dosing interval;
- a mean plasma concentration from about 59 to about 322 pg/ml at about 24 hours after initiation of the dosing interval;
- a mean plasma concentration from about 102 to about 377 pg/ml at about 36 hours after initiation of the dosing interval;
- a mean plasma concentration from about 124 to about 492 pg/ml at about 48 hours after initiation of the dosing interval;
- a mean plasma concentration from about 159 to about 492 pg/ml at about 60 hours after initiation of the dosing interval;
- a mean plasma concentration from about 169 to about 526 pg/ml at about 60 hours after initiation of the dosing interval;
- thereafter administering the buprenorphine in a manner such that the mean plasma concentrations are maintained from about 153 to about 526 pg/ml over at least the next 48 hours.
A method of effectively treating pain in humans, comprising
- administering buprenorphine to human patients in a manner such that the following mean plasma concentrations are achieved over a 72 hour dosing interval:
- a mean plasma concentration from about 4 to about 85 pg/ml at about 6 hours after initiation of the dosing interval;
- a mean plasma concentration from about 42 to about 222 pg/ml at about 12 hours after initiation of the dosing interval;
- a mean plasma concentration from about 89 to about 483 pg/ml at about 24 hours after initiation of the dosing interval;
- a mean plasma concentration from about 152 to about 565 pg/ml at about 36 hours after initiation of the dosing interval;
- a mean plasma concentration from about 186 to about 738 pg/ml at about 48 hours after initiation of the dosing interval;
- a mean plasma concentration from about 238 to about 738 pg/ml at about 48 hours after initiation of the dosing interval;
- a mean plasma concentration from about 254 to about 789 pg/ml at about 60 hours after initiation of the dosing interval;
- thereafter administering the buprenorphine in a manner such that the mean plasma concentrations are maintained from about 230 to about 789 pg/ml over at least the next 48 hours.
A method of effectively treating pain in humans, comprising
- administering buprenorphine to human patients in a manner such that the following mean plasma concentrations are achieved over a 72 hour dosing interval:
- a mean plasma concentration from about 5 to about 113 pg/ml at about 6 hours after initiation of the dosing interval;
- a mean plasma concentration from about 55 to about 296 pg/ml at about 12 hours after initiation of the dosing interval;
- a mean plasma concentration from about 118 to about 644 pg/ml at about 24 hours after initiation of the dosing interval;
- a mean plasma concentration from about 203 to about 753 pg/ml at about 36 hours after initiation of the dosing interval;
- a mean plasma concentration from about 247 to about 984 pg/ml at about 48 hours after initiation of the dosing interval;
- a mean plasma concentration from about 317 to about 984 pg/ml at about 60 hours after initiation of the dosing interval;
- a mean plasma concentration from about 339 to about 1052 pg/ml at about 72 hours after initiation of the dosing interval;
- and
- thereafter administering the buprenorphine in a manner such that the mean plasma concentrations are maintained from about 306 to about 1052 pg/ml over at least the next 48 hours.
A method of effectively treating pain in humans, comprising administering buprenorphine transdermally to human patients such that mean relative release rates are achieved over a dosing interval as follows:
- a mean relative release rate of from about 3 ug/hr to about 86 ug/hr from the initiation of the dosing interval until about 72 hours after the initiation of the dosing interval;
- and
- a mean relative release rate of about 0.3 ug/hr to about 9 ug/hr from about 72 hours after the initiation of the dosing interval until the end of the dosing interval.
A method of effectively treating pain in humans, comprising
- applying transdermal delivery systems containing buprenorphine as the active ingredient onto the skin of patients which provide a substantially first order release rate of buprenorphine over a first three-day dosing interval, such that a mean plasma concentration from about 21 to about 1052 pg/ml is attained about 72 hours after application of said transdermal delivery system;
- and maintaining said transdermal delivery systems on the skin of the patients for at least an additional two-day dosing interval during which said transdermal delivery system provides substantially zero order kinetics, such that a mean relative release rate from about 0.3 g/hr to about 9 g/hr is maintained over said at least two-day additional dosing interval and the patients experience analgesia throughout the at least two-day additional dosing interval.
A method of effectively treating pain in humans, comprising
- applying a transdermal delivery system containing buprenorphine as the active ingredient onto the skin of patients which provide a first order release rate of buprenorphine over a three-day dosing interval, such that a maximum plasma concentration from about 20 pg/ml to about 1052 pg/ml is attained, and
- maintaining said transdermal delivery systems on the skin of the patients for at least an additional two-day dosing interval during which said transdermal delivery system provides substantially zero order kinetics, such that the patients experience, analgesia throughout the at least two-day additional dosing interval.
A method of treating human patients suffering from moderate to severe pain by applying a transdermal delivery system containing buprenorphine onto the skin of the patient and maintaining the transdermal delivery system in contact with the skin for a 3 day dosing interval, the transdermal delivery system containing an amount of buprenorphine sufficient to maintain an adequate relative release rate to provide effective analgesia in the patient for approximately only 3 days, comprising maintaining the transdermal delivery system in contact with the patient's skin for at least 2 to about 5 additional days beyond said 3 day dosing interval, such that the patient continues to receive effective analgesia from said transdermal buprenorphine delivery system.
In a method of treating human patients suffering from moderate to severe pain by applying a transdermal delivery system containing buprenorphine onto the skin of the patient and maintaining the transdermal delivery system in contact with the skin for a 3 day dosing interval, the transdermal delivery system containing an amount of buprenorphine sufficient to maintain an adequate relative release rate to provide effective analgesia in the patient for about 3 days, the improvement comprising maintaining the transdermal delivery system in contact with the patient's skin for at least 2 to about 5 additional days beyond said 3 day dosing interval, wherein maximal analgesia is experienced by the patient prior to attainment of peak plasma buprenorphine concentrations.
A method of treating human patients suffering from opioid addiction by applying a transdermal delivery system containing buprenorphine onto the skin of the patient and maintaining the transdermal delivery system in contact with the skin for a 3 day dosing interval, the transdermal delivery system containing an amount of buprenorphine sufficient to maintain an adequate relative release rate to provide a plasma concentration of from about 1000 pg/ml to about 10,000 pg/ml at the end of said 3 day dosing interval, and maintaining the transdermal delivery system in contact with the patient's skin for at least 2 to about 5 additional days beyond said 3 day dosing interval, such that the patient continues to receive effective treatment for opioid addiction from said transdermal buprenorphine delivery system over said dosing interval.
Dependencies are inferred from the claim text.