Buprenorphine dosing regimens

Abstract

The disclosure provides a dosage regimen using sustained-release buprenorphine formulations to produce therapeutic levels of buprenorphine in patients for the treatment of pain or opioid use disorders.

1 .- 67 . (canceled) 
     
     
         68 . A method of treating opioid use disorder in a human in need thereof, the method comprising:
 (a) administering to the human, by injection once per month for two months, a first composition comprising: (i) about 300 mg of buprenorphine or a pharmaceutically acceptable salt thereof, and (ii) a first means for achieving sustained release of the buprenorphine or pharmaceutically acceptable salt thereof; and   (b) administering to the human, by injection once per month beginning with a third month and for at least four months, a second composition comprising: (i) about 100 mg of buprenorphine or a pharmaceutically acceptable salt thereof; and (ii) a second means for achieving sustained release of the buprenorphine or pharmaceutically acceptable salt thereof.   
     
     
         69 . The method of  claim 68 , wherein the buprenorphine is in the form of a free base. 
     
     
         70 . The method of  claim 68 , wherein the method produces an average buprenorphine plasma concentration of at least 2 ng/mL. 
     
     
         71 . The method of  claim 68 , wherein the method produces an average buprenorphine plasma concentration of about 2 ng/mL to about 5 ng/mL. 
     
     
         72 . The method of  claim 68 , wherein the method produces a μ-opioid receptor occupancy as measured by a maximum effect model of Equation 1 of at least 70%. 
     
     
         73 . The method of  claim 68 , wherein the injection is a subcutaneous injection. 
     
     
         74 . The method of  claim 68 , wherein the method of treating opioid use disorder is a method of suppressing opioid withdrawal signs and symptoms. 
     
     
         75 . The method of  claim 68 , wherein the opioid use disorder is moderate opioid use disorder or severe opioid use disorder. 
     
     
         76 . The method of  claim 68 , wherein the buprenorphine or pharmaceutically acceptable salt thereof is present in the first composition and/or the second composition in an amount of between about 5 wt % and about 30 wt %. 
     
     
         77 . The method of  claim 68 , wherein the buprenorphine or pharmaceutically acceptable salt thereof is present in the first composition and/or the second composition in an amount of about 14 wt % to about 22 wt %. 
     
     
         78 . The method of  claim 68 , wherein the buprenorphine or pharmaceutically acceptable salt thereof is present in the first composition and/or the second composition in an amount of about 18 wt %. 
     
     
         79 . the method of  claim 68 , wherein the first means and the second means are the same. 
     
     
         80 . The method of  claim 68 , further comprising transmucosally administering to the patient a composition comprising buprenorphine or a pharmaceutically acceptable salt thereof prior to (a). 
     
     
         81 . The method of  claim 68 , further comprising sublingually administering to the patient a composition comprising buprenorphine prior to (a). 
     
     
         82 . The method of  claim 68 , further comprising inducting and stabilizing the patient on a transmucosal composition comprising buprenorphine prior to (a). 
     
     
         83 . The method of  claim 68 , further comprising inducting and stabilizing the patient on a sublingual composition comprising buprenorphine prior to (a). 
     
     
         84 . A method of treating opioid addiction in a human in need thereof, the method comprising:
 (a) transmucosally administering a composition comprising buprenorphine or a pharmaceutically acceptable salt thereof;   (b) subcutaneously administering, once per month for two months, a first composition comprising: (i) about 300 mg of buprenorphine free base; and (ii) a first means for achieving sustained release of the buprenorphine; and   (c) subcutaneously administering, once per month beginning with a third month and for at least four months, a second composition comprising: (i) about 100 mg of buprenorphine free base; and (ii) a second means for achieving sustained release of the buprenorphine.   
     
     
         85 . The method of  claim 84 , wherein the buprenorphine or pharmaceutically acceptable salt thereof is present in the first composition and/or the second composition in an amount of between about 5 wt % and about 30 wt %. 
     
     
         86 . The method of  claim 84 , wherein the buprenorphine or pharmaceutically acceptable salt thereof is present in the first composition and/or the second composition in an amount of about 18 wt %. 
     
     
         87 . The method of  claim 84 , wherein the first means and the second means are the same.