Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome

Abstract

Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions. The oral bioavailability of zoledronic acid can be enhanced by administering the zoledronic acid in the disodium salt form

1 . A method of treating complex regional pain syndrome (CRPS) comprising orally administering about 150 mg to about 200 mg of zoledronic acid about every two weeks to a human being in need thereof, wherein the human being receives a total of about 400 mg to about 500 mg of zoledronic acid within a period of six months. 
     
     
         2 . The method of  claim 1 , wherein the AUC of zoledronic acid is about 300 ng·hr/mL to about 350 ng·hr/mL. 
     
     
         3 . The method of  claim 2 , wherein the AUC of zoledronic acid is measured over a period of 24 hours. 
     
     
         4 . The method of  claim 1 , wherein the AUC of zoledronic acid is about 300 ng·hr/mL to about 310 ng·hr/mL. 
     
     
         5 . The method of  claim 4 , wherein the AUC of zoledronic acid is measured over a period of 24 hours. 
     
     
         6 . The method of  claim 1 , wherein the AUC of zoledronic acid is about 200 ng·hr/mL to about 300 ng·hr/mL. 
     
     
         7 . The method of  claim 6 , wherein the AUC of zoledronic acid is measured over a period of 24 hours. 
     
     
         8 . The method of  claim 1 , wherein the CRPS is linked to a traumatic or inciting event. 
     
     
         9 . The method of  claim 1 , wherein the human being has suffered from CRPS for at least 2 months. 
     
     
         10 . The method of  claim 1 , wherein the human being has a numeric rating scale (NRS) score of 4 or greater, measured using a scale of 0 to 10, prior to treatment. 
     
     
         11 . The method of  claim 1 , wherein the human being has a numeric rating scale (NRS) score of 5 or greater, measured using a scale of 0 to 10, prior to treatment. 
     
     
         12 . The method of  claim 1 , wherein the treatment results in the human being having a decrease in a numerical rating scale (NRS) score of at least about 0.8, measured using a scale of 0 to 10. 
     
     
         13 . The method of  claim 1 , wherein the treatment results the human being having a decrease in a numerical rating scale (NRS) score of at least about 1.5, measured using a scale of 0 to 10. 
     
     
         14 . The method of  claim 1 , wherein three doses of about 150 mg to about 165 mg of zoledronic acid are administered. 
     
     
         15 . The method of  claim 1 , wherein zoledronic acid is administered in a manner that results in a bioavailability of zoledronic acid of about 1% to about 3%. 
     
     
         16 . The method of  claim 1 , further comprising administering to the human being a non-steroidal anti-inflammatory drug (NSAID), opioid, or other pain medication. 
     
     
         17 . The method of  claim 1 , wherein the human being experiences at least about a 10% pain reduction. 
     
     
         18 . A method of treating complex regional pain syndrome (CRPS) comprising orally administering about 100 mg to about 200 mg of zoledronic acid in at least two divided doses to a human being in need thereof, wherein the human being receives a total of about 300 mg to about 500 mg of zoledronic acid within a period of six months. 
     
     
         19 . The method of  claim 18 , wherein the CRPS is linked to a traumatic or inciting event. 
     
     
         20 . The method of  claim 18 , wherein zoledronic acid is administered in an imidazolium salt form. 
     
     
         21 . The method of  claim 18 , wherein zoledronic acid is administered at least twice within a period of a month. 
     
     
         22 . The method of  claim 18 , wherein the bioavailability of zoledronic acid is about 0.1% to about 5%. 
     
     
         23 . The method of  claim 18 , wherein the treatment results in the human being having a decrease in a numerical rating scale (NRS) score of at least about 0.8, measured using a scale of 0 to 10. 
     
     
         24 . The method of  claim 18 , wherein the treatment results the human being having a decrease in a numerical rating scale (NRS) score of at least about 1.5, measured using a scale of 0 to 10. 
     
     
         25 . A method of treating complex regional pain syndrome (CRPS) comprising orally administering about 160 mg of zoledronic acid three times to a human being in need thereof within a period of six months, wherein zoledronic acid is administered no more frequently than once a week. 
     
     
         26 . The method of  claim 25 , wherein the 160 mg doses of zoledronic acid are administered about 14 days apart. 
     
     
         27 . The method of  claim 25 , wherein the CRPS is linked to a traumatic or inciting event. 
     
     
         28 . The method of  claim 25 , wherein the dosage form administered to the human being is about 1% (w/w) to about 50% (w/w) zoledronic acid. 
     
     
         29 . The method of  claim 25 , wherein the human being has a numeric rating scale (NRS) score of 4 or greater, measured using a scale of 0 to 10, prior to treatment. 
     
     
         30 . The method of  claim 25 , wherein the human being has a numeric rating scale (NRS) score of 5 or greater, measured using a scale of 0 to 10, prior to treatment.