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US 5,968,547 AGranted
Method of providing sustained analgesia with buprenorphine
AssigneeEuro-Celtique S.A.
InventorsRobert F. Reder, Paul D. Goldenheim, Robert F. Kaiko
Life of this patent
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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.
Claims47
A method of treating pain in a human patient, comprising
- administering buprenorphine transdermally to said human patient 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, said transdermal delivery system maintaining a mean relative release rate of from about 3 ug/hr to about 86 ug/hr and providing a substantially first order plasma level increase of buprenorphine 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 and providing a substantially zero order plasma level fluctuation of buprenorphine from about 72 hours after the initiation of the dosing interval until the end of at least the five-day dosing interval, such that the following mean plasma concentrations are achieved:
- 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
- a mean plasma concentration from about 19 to about 1052 pg/ml over at least the next 48 hours.
8 more elements
A method of treating pain in a human patient, comprising
- administering buprenorphine transdermally to said human patient 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, said transdermal delivery system maintaining a mean relative release rate of from about 13 ug/hr to about 21 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 1 ug/hr to about 2 ug/hr from about 72 hours after the initiation of the dosing interval until the end of at least the five-day dosing interval, such that the following mean plasma concentrations are achieved:
- 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
- a mean plasma concentration from about 77 to about 263 pg/ml over at least the next 48 hours.
8 more elements
A method of treating pain in a human patient, comprising
- administering buprenorphine transdermally to said human patient 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, said transdermal delivery system maintaining a mean relative release rate of from about 3 ug/hr to about 5 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 0.6 ug/hr from about 72 hours after the initiation of the dosing interval until the end of at least the five-day dosing interval, such that the following mean plasma concentrations are achieved:
- 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
- a mean plasma concentration from about 19 to about 66 pg/ml over at least the next 48 hours.
8 more elements
A method of treating pain in a human patient, comprising
- administering buprenorphine transdermally to said human patient 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, said transdermal delivery system maintaining a mean relative release rate of from about 6 ug/hr to about 11 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 0.7 ug/hr to about 1 ug/hr from about 72 hours after the initiation of the dosing interval until the end of at least the five-day dosing interval, such that the following mean plasma concentrations are achieved:
- 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
- a mean plasma concentration from about 38 to about 132 pg/ml over at least the next 48 hours.
8 more elements
A method of treating pain in a human patient, comprising
- administering buprenorphine transdermally to said human patient 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, said transdermal delivery system maintaining a mean relative release rate of from about 26 ug/hr to about 43 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 2 ug/hr to about 4 ug/hr from about 72 hours after the initiation of the dosing interval until the end of at least the five-day dosing interval, such that the following mean plasma concentrations are achieved:
- 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;
- a mean plasma concentration from about 153 to about 526 pg/ml over at least the next 48 hours.
7 more elements
A method of treating pain in a human patient, comprising
- administering buprenorphine transdermally to said human patient 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, said transdermal delivery system maintaining a mean relative release rate of from about 38 ug/hr to about 64 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 4 ug/hr to about 7 ug/hr from about 72 hours after the initiation of the dosing interval until the end of at least the five-day dosing interval, such that the following mean plasma concentrations are achieved:
- 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;
- a mean plasma concentration from about 230 to about 789 pg/ml over at least the next 48 hours.
7 more elements
A method of treating pain in a human patient, comprising
- administering buprenorphine transdermally to said human patient 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, said transdermal delivery system maintaining a mean relative release rate of from about 51 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 5 ug/hr to about 9 ug/hr from about 72 hours after the initiation of the dosing interval until the end of at least the five-day dosing interval, such that the following mean plasma concentrations are achieved:
- 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
- a mean plasma concentration from about 306 to about 1052 pg/ml over at least the next 48 hours.
8 more elements
A method of treating pain in a human patient, comprising
- administering buprenorphine transdermally to said human patient 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.
1 more element
A method of treating pain in a human patient, comprising
- applying a transdermal delivery system containing buprenorphine as the active ingredient onto the skin of said human patient to provide a substantially first order plasma level increase 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 system on the skin of said human patient for at least an additional two-day dosing interval, such that a mean relative release rate from about 0.3 .mu.g/hr to about 9 .mu.g/hr is maintained over said at least two-day additional dosing interval and said transdermal delivery system provides a therapeutic effect to said human patient throughout the at least two-day additional dosing interval.
A method of treating pain in a human patient, comprising
- applying a transdermal delivery system containing buprenorphine as the active ingredient onto the skin of said human patient to 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 said human patient for at least an additional two-day dosing interval during which said transdermal delivery system provides substantially zero order kinetics, such that said transdermal delivery system provides a therapeutic effect to said human patient throughout the at least two-day additional dosing interval.
A method of treating a human patient suffering from moderate to severe pain by applying a transdermal delivery system containing buprenorphine onto the skin of the human 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 therapeutic effect in the patient for approximately only 3 days, comprising maintaining the transdermal delivery system in contact with the human patient's skin for at least 2 to about 5 additional days beyond said 3 day dosing interval, such that the human patient continues to receive a therapeutic effect from said transdermal buprenorphine delivery system.
In a method of treating a human patient suffering from moderate to severe pain by applying a transdermal delivery system containing buprenorphine onto the skin of the human 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 therapeutic effect in the patient for about 3 days, the improvement comprising maintaining the transdermal delivery system in contact with the human patient's skin for at least 2 to about 5 additional days beyond said 3 day dosing interval.
Dependencies are inferred from the claim text.