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

Abstract

Oral dosage forms of osteoclast inhibitors, such as nitrogen-containing bisphosphonates, can be used to treat or alleviate pain or related conditions such as complex regional pain syndrome.

What is claimed is: 
     
         1 . A method of treating pain associated with complex regional pain syndrome comprising orally administering a dosage form comprising zoledronic acid in an acid form or a salt form to a human being suffering from complex regional pain syndrome;
 wherein the human being has an identifiable inciting trauma associated with the complex regional pain syndrome;   wherein the dosage form is free of bioavailability enhancing agents to the extent that the bioavailability of zoledronic acid in the dosage form is no higher than the bioavailability of an orally administered unenhanced disodium salt of zoledronic acid; and   wherein about 0.4 mg/kg to about 2.8 mg/kg of zoledronic acid is orally administered to the human being 2 to 10 times at a frequency of about once weekly to about once a month.   
     
     
         2 . The method of  claim 1 , wherein about 1.3 mg/kg to about 2.8 mg/kg of zoledronic acid in the acid form or the salt form, based upon the weight of the diacid form, is orally administered to the human being 2, 3, 4, or 5 times at a frequency of about once every 2 weeks to about once every four weeks. 
     
     
         3 . The method of  claim 1 , wherein about 1.3 mg/kg to about 2.7 mg/kg of zoledronic acid in the acid form or the salt form, based upon the weight of the diacid form, is orally administered to the human being 3 times at a frequency of about once every 2 weeks. 
     
     
         4 . The method of  claim 1 , wherein about 0.4 mg/kg to about 0.9 mg/kg of zoledronic acid in the acid form or the salt form, based upon the weight of the diacid form, is orally administered to the human being 3, 4, 5, 6, 7, or 8 times at a frequency of about once a week. 
     
     
         5 . The method of  claim 1 , wherein a total of about 300 mg of zoledronic acid in the acid form or the salt form, based upon the weight of the diacid form, is orally administered to the human being within a period of six months. 
     
     
         6 . The method of  claim 1 , wherein a total of about 150 mg of zoledronic acid in the acid form or the salt form, based upon the weight of the diacid form, is orally administered to the human being within a period of six months. 
     
     
         7 . The method of  claim 1 , wherein about 480 mg of zoledronic acid in the acid form or the salt form, based upon the weight of the diacid form, is orally administered to the human being in about one month, in three approximately equal oral administrations occurring at an interval of about 2 weeks. 
     
     
         8 . The method of  claim 1 , wherein about 0.4 mg/kg to about 0.9 mg/kg of zoledronic acid in the acid form or the salt form, based upon the weight of the diacid form, is orally administered to the human being 6 times at a frequency of about once a week. 
     
     
         9 . The method of  claim 1 , wherein about 0.4 mg/kg to about 0.9 mg/kg of zoledronic acid in the acid form or the salt form, based upon the weight of the diacid form, is orally administered to the human being 3 times at a frequency of about once a week. 
     
     
         10 . The method of  claim 1 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of at least about 30 ng/mL. 
     
     
         11 . The method of  claim 1 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 30 ng/mL to about 50 ng/mL. 
     
     
         12 . The method of  claim 8 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 30 ng/mL to about 40 ng/mL. 
     
     
         13 . The method of  claim 9 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 30 ng/mL to about 40 ng/mL. 
     
     
         14 . The method of  claim 1 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 30 ng/mL to about 100 ng/mL. 
     
     
         15 . The method of  claim 1 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 50 ng/mL to about 150 ng/mL. 
     
     
         16 . The method of  claim 7 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 50 ng/mL to about 100 ng/mL. 
     
     
         17 . The method of  claim 7 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 50 ng/mL to about 80 ng/mL. 
     
     
         18 . The method of  claim 7 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 80 ng/mL to about 120 ng/mL. 
     
     
         19 . The method of  claim 7 , wherein orally administering zoledronic acid in the acid form or the salt form to the human being results in a C max  of zoledronic acid of about 120 ng/mL to about 200 ng/mL. 
     
     
         20 . The method of  claim 4 , wherein the zoledronic acid in the acid form or the salt form is at least 20% of the weight of the dosage form. 
     
     
         21 . The method of  claim 12 , wherein the zoledronic acid in the acid form or the salt form is at least 20% of the weight of the dosage form. 
     
     
         22 . The method of  claim 13 , wherein the zoledronic acid in the acid form or the salt form is at least 20% of the weight of the dosage form. 
     
     
         23 . The method of  claim 4 , wherein the zoledronic acid in the acid form or the salt form is about 20% to about 30% of the weight of the dosage form. 
     
     
         24 . The method of  claim 4 , wherein the zoledronic acid in the acid form or the salt form is about 30% to about 50% of the weight of the dosage form. 
     
     
         25 . The method of  claim 4 , wherein the zoledronic acid in the acid form or the salt form is about 50% to about 80% of the weight of the dosage form. 
     
     
         26 . The method of  claim 4 , wherein the zoledronic acid in the acid form or the salt form is about 80% to about 90% of the weight of the dosage form. 
     
     
         27 . The method of  claim 7 , wherein the zoledronic acid in the acid form or the salt form is at least 20% of the weight of the dosage form. 
     
     
         28 . The method of  claim 7 , wherein the zoledronic acid in the acid form or the salt form is at least 50% of the weight of the dosage form. 
     
     
         29 . The method of  claim 1 , wherein the imidazole ring of the zoledronic acid salt is in an imidazolium form. 
     
     
         30 . The method of  claim 7 , wherein the imidazole ring of the zoledronic acid salt is in an imidazolium form.