Methods for concomitant treatment of theophylline and febuxostat

Abstract

The present disclosure relates to a method of treating hyperuricemia in a patient that also suffers from a second disease state requiring treatment with theophylline, wherein the patient receives concomitant treatment with a xanthine oxidoreductase inhibitor and theophylline without resulting in theophylline toxicity to the patient and without substantial adjustments to the manufacturer's recommended dosage of theophylline.

What is claimed is: 
     
         1 . A method of treating hyperuricemia in a patient in need of treatment thereof, the method comprising the steps of:
 administering to a patient suffering from hyperuricemia and at least one second disease state, a therapeutically effective amount of at least one xanthine oxidoreductase inhibitor, wherein the subject is also receiving concomitant administration of theophylline to treat the at least one second disease state, and   further wherein (i) the administration of the at least one xanthine oxidoreductase inhibitor to the patient does not result in theophylline toxicity to the patient; and (ii) administration of the theophylline is in an amount ranging from about 90% to about 110% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor.   
     
     
         2 . The method of  claim 1 , wherein the second disease state comprises chronic obstructive pulmonary disease, asthma, chronic bronchitis, emphysema, neonatal apnea, neonatal bradycardia, and combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein the patient is further suffering from at least one third disease state, wherein the third disease comprises gout, hypertension, chronic stable angina, renal failure, nephrolithiasis, acute gouty arthritis, chronic gouty joint disease, tophaceous gout, uric acid urolithiasis, uric acid nephropathy, progressive renal disease, and combinations thereof. 
     
     
         4 . The method of  claim 1 , wherein the theophylline dosage amount ranges from about 95% to about 105% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor. 
     
     
         5 . The method of  claim 1 , wherein the xanthine oxidoreductase inhibitor is selected from the group consisting of: 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid, 2-[3-cyano-4-(3-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-[3-cyano-4-(2-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-(3-cyano-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid, 2-[4-(2-carboxypropoxy)-3-cyanophenyl]-4-methyl-5-thiazolecarboxylic acid, 1-(3-cyano-4-(2,2-dimethylpropoxy)phenyl)-1H-pyrazole-4-carboxylic acid, 1-3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid, pyrazolo[1,5-a]-1,3,5-triazin-4-(1H)-one, 8-[3-methoxy-4-(phenylsulfinyl)phenyl]-sodium salt (±), 3-(2-methyl-4-pyridyl)-5-cyano-4-isobutoxyphenyl)-1,2,4-triazole, and pharmaceutically acceptable salts thereof. 
     
     
         6 . A method of treating hyperuricemia in a patient in need of treatment thereof, the method comprising the steps of:
 administering to a patient suffering from hyperuricemia and at least one second disease state, a therapeutically effective amount at least one xanthine oxidoreductase inhibitor, wherein said subject will also be receiving a concomitant administration of theophylline to treat the at least one second disease state, and   further wherein (i) the administration of the at least one xanthine oxidoreductase inhibitor to said patient will not result in theophylline toxicity to said patient; and (ii) administration of the theophylline will be in an amount ranging from about 90% to about 110% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor.   
     
     
         7 . The method of  claim 6 , wherein the second disease state comprises chronic obstructive pulmonary disease, asthma, chronic bronchitis, emphysema, neonatal apnea, neonatal bradycardia, and combinations thereof. 
     
     
         8 . The method of  claim 6 , wherein the theophylline dosage amount ranges from about 95% to about 105% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor. 
     
     
         9 . The method of  claim 6 , wherein the second disease state comprises chronic obstructive pulmonary disease, asthma, chronic bronchitis, emphysema, neonatal apnea, neonatal bradycardia, and combinations thereof. 
     
     
         10 . The method of  claim 6 , wherein the patient is further suffering from at least one third disease state, wherein the third disease comprises gout, hypertension, chronic stable angina, renal failure, nephrolithiasis, acute gouty arthritis, chronic gouty joint disease, tophaceous gout, uric acid urolithiasis, uric acid nephropathy, progressive renal disease, and combinations thereof. 
     
     
         11 . The method of  claim 6 , wherein the theophylline dosage amount ranges from about 95% to about 105% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor. 
     
     
         12 . The method of  claim 6 , wherein the xanthine oxidoreductase inhibitor is selected from the group consisting of: 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid, 2-[3-cyano-4-(3-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-[3-cyano-4-(2-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-(3-cyano-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid, 2-[4-(2-carboxypropoxy)-3-cyanophenyl]-4-methyl-5-thiazolecarboxylic acid, 1-(3-cyano-4-(2,2-dimethylpropoxy)phenyl)-1H-pyrazole-4-carboxylic acid, 1-3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid, pyrazolo[1,5-a]-1,3,5-triazin-4-(1H)-one, 8-[3-methoxy-4-(phenylsulfinyl)phenyl]-sodium salt (±), 3-(2-methyl-4-pyridyl)-5-cyano-4-isobutoxyphenyl)-1,2,4-triazole, and pharmaceutically acceptable salts thereof. 
     
     
         13 . The method of  claim 6 , wherein the patient suffering from hyperuricemia and the at least one second disease state initiates treatment with theophylline concurrently with the xanthine oxidoreductase inhibitor, or subsequent to the initiation of treatment with the xanthine oxidoreductase inhibitor. 
     
     
         14 . The method of  claim 6 , wherein the patient suffering from hyperuricemia and the at least one second disease state is previously administered theophylline prior to initiation of treatment with the xanthine oxidoreductase inhibitor. 
     
     
         15 . A method of treating a patient suffering from at least one first disease state and in need of treatment thereof, the method comprising the step of:
 administering to a patient suffering from at least one first disease state and at least one second disease state, a therapeutically effective amount of at least one xanthine oxidoreductase inhibitor, wherein the subject is also receiving concomitant administration of theophylline to treat the at least one second disease state, and   further wherein (i) the administration of the at least one xanthine oxidoreductase inhibitor to the patient does not result in theophylline toxicity to the patient; and (ii) administration of the theophylline is in an amount ranging from about 90% to about 110% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor.   
     
     
         16 . The method of  claim 15 , wherein the first disease state is gout, prostatitis, inflammatory bowel disease, QT interval prolongation, myocardial infarction, cardiac hypertrophy, hypertension, nephrolithiasis, renal impairment, chronic kidney disease, metabolic syndrome, diabetes, diabetic nephropathy, congestive heart failure or combinations thereof. 
     
     
         17 . The method of  claim 15 , wherein the second disease state comprises chronic obstructive pulmonary disease, asthma, chronic bronchitis, emphysema, neonatal apnea, neonatal bradycardia, and combinations thereof. 
     
     
         18 . The method of  claim 15 , wherein the patient is further suffering from at least one third disease state, wherein the third disease comprises gout, hypertension, chronic stable angina, renal failure, nephrolithiasis, acute gouty arthritis, chronic gouty joint disease, tophaceous gout, uric acid urolithiasis, uric acid nephropathy, progressive renal disease, and combinations thereof. 
     
     
         19 . The method of  claim 15 , wherein the theophylline dosage amount ranges from about 95% to about 105% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor. 
     
     
         20 . The method of  claim 15 , wherein the xanthine oxidoreductase inhibitor is selected from the group consisting of: 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid, 2-[3-cyano-4-(3-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-[3-cyano-4-(2-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-(3-cyano-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid, 2-[4-(2-carboxypropoxy)-3-cyanophenyl]-4-methyl-5-thiazolecarboxylic acid, 1-(3-cyano-4-(2,2-dimethylpropoxy)phenyl)-1H-pyrazole-4-carboxylic acid, 1-3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid, pyrazolo[1,5-a]-1,3,5-triazin-4-(1H)-one, 8-[3-methoxy-4-(phenylsulfinyl)phenyl]-sodium salt (±), 3-(2-methyl-4-pyridyl)-5-cyano-4-isobutoxyphenyl)-1,2,4-triazole, and pharmaceutically acceptable salts thereof. 
     
     
         21 . A method of treating hyperuricemia in a patient suffering from gout and in need of treatment thereof, the method comprising the step of:
 administering to a patient suffering from gout and hyperuricemia and at least one third disease state, a therapeutically effective amount of at least one xanthine oxidoreductase inhibitor, wherein the subject is also receiving concomitant administration of theophylline to treat the at least one third disease state, and   further wherein (i) the administration of the at least one xanthine oxidoreductase inhibitor to the patient does not result in theophylline toxicity to the patient; and (ii) administration of the theophylline is in an amount ranging from about 90% to about 110% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor.   
     
     
         22 . The method of  claim 21 , wherein the third disease state comprises chronic obstructive pulmonary disease, asthma, chronic bronchitis, emphysema, neonatal apnea, neonatal bradycardia, and combinations thereof. 
     
     
         23 . The method of  claim 21 , wherein the patient is further suffering from at least one fourth disease state, wherein the fourth disease state is hypertension, chronic stable angina, renal failure, nephrolithiasis, acute gouty arthritis, chronic gouty joint disease, tophaceous gout, uric acid urolithiasis, uric acid nephropathy, progressive renal disease, and combinations thereof. 
     
     
         24 . The method of  claim 21 , wherein the theophylline dosage amount ranges from about 95% to about 105% of a manufacturer's recommended theophylline dosage amount in the absence of administration of at least one xanthine oxidoreductase inhibitor. 
     
     
         25 . The method of  claim 21 , wherein the xanthine oxidoreductase inhibitor is selected from the group consisting of: 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid, 2-[3-cyano-4-(3-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-[3-cyano-4-(2-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-(3-cyano-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid, 2-[4-(2-carboxypropoxy)-3-cyanophenyl]-4-methyl-5-thiazolecarboxylic acid, 1-(3-cyano-4-(2,2-dimethylpropoxy)phenyl)-1H-pyrazole-4-carboxylic acid, 1-3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid, pyrazolo[1,5-a]-1,3,5-triazin-4-(1H)-one, 8-[3-methoxy-4-(phenylsulfinyl)phenyl]-sodium salt (±), 3-(2-methyl-4-pyridyl)-5-cyano-4-isobutoxyphenyl)-1,2,4-triazole, and pharmaceutically acceptable salts thereof. 
     
     
         26 . The method of  claim 21 , wherein the patient suffering from gout and hyperuricemia and the at least one third disease state initiates treatment with theophylline concurrently with the xanthine oxidoreductase inhibitor, or subsequent to the initiation of treatment with the xanthine oxidoreductase inhibitor. 
     
     
         27 . The method of  claim 21 , wherein the patient suffering from gout and hyperuricemia and the at least one third disease state is previously administered theophylline prior to initiation of treatment with the xanthine oxidoreductase inhibitor.