Methods of improving myocardial performance in fontan patients using udenafil compositions

Abstract

The present invention relates generally to the field of using udenafil or a pharmaceutically acceptable salt thereof in patients who have undergone the Fontan operation.

1 - 30 . (canceled) 
     
     
         31 . A method of treating a single ventricle heart disease (SVHD) patient with udenafil, or a pharmaceutically acceptable salt thereof, wherein the SVHD patient is in need of udenafil treatment, the method comprising:
 administering an effective amount of udenafil, or a pharmaceutically acceptable salt thereof, to the SVHD patient.   
     
     
         32 . The method of  claim 31 , wherein the SVHD patient is at least 12 years old. 
     
     
         33 . The method of  claim 31 , wherein the SVHD patient is a female. 
     
     
         34 . The method of  claim 32 , wherein the SVHD patient is a female. 
     
     
         35 . The method of  claim 31 , wherein the SVHD patient is a male. 
     
     
         36 . The method of  claim 32 , wherein the SVHD patient is a male. 
     
     
         37 . The method of  claim 31 , wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage form. 
     
     
         38 . The method of  claim 37 , wherein the oral dosage form is a tablet. 
     
     
         39 . The method of  claim 37 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         40 . A method of daily treating a single ventricle heart disease (SVHD) patient with udenafil, or a pharmaceutically acceptable salt thereof, wherein the SVHD patient has the superior and inferior vena cavae attached to the pulmonary arteries and is in need of udenafil treatment, the method comprising:
 administering an effective amount of udenafil, or a pharmaceutically acceptable salt thereof, to the SVHD patient to treat the SVHD patient in accordance with a daily treatment regimen.   
     
     
         41 . The method of  claim 40 , wherein the SVHD patient is at least 12 years old. 
     
     
         42 . The method of  claim 40 , wherein the SVHD patient is a female. 
     
     
         43 . The method of  claim 41 , wherein the SVHD patient is a female. 
     
     
         44 . The method of  claim 40 , wherein the SVHD patient is a male. 
     
     
         45 . The method of  claim 41 , wherein the SVHD patient is a male. 
     
     
         46 . The method of  claim 40 , wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage form. 
     
     
         47 . The method of  claim 46 , wherein the oral dosage form is a tablet. 
     
     
         48 . The method of  claim 46 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         49 . A method of daily treating a single ventricle heart disease (SVHD) patient with udenafil, or a pharmaceutically acceptable salt thereof, wherein the SVHD patient has Fontan physiology and who is in need of udenafil treatment, the method comprising:
 administering an effective amount of udenafil, or a pharmaceutically acceptable salt thereof, to the SVHD patient to treat the SVHD patient in accordance with a daily treatment regimen.   
     
     
         50 . The method of  claim 49 , wherein the SVHD patient is at least 12 years old. 
     
     
         51 . The method of  claim 49 , wherein the SVHD patient is a female. 
     
     
         52 . The method of  claim 50 , wherein the SVHD patient is a female. 
     
     
         53 . The method of  claim 49 , wherein the SVHD patient is a male. 
     
     
         54 . The method of  claim 50 , wherein the SVHD patient is a male. 
     
     
         55 . The method of  claim 49 , wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage form. 
     
     
         56 . The method of  claim 55 , wherein the oral dosage form is a tablet. 
     
     
         57 . The method of  claim 55 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         58 . A method of treating a Fontan patient who has undergone a Fontan procedure and who has Fontan physiology in the management of a single ventricle heart defect (SVHD), wherein the Fontan patient is in need of treatment for SVHD, the method comprising:
 administering an effective amount of udenafil, or a pharmaceutically acceptable salt thereof, to the Fontan patient to manage the Fontan patient's SVHD in accordance with a treatment regimen.   
     
     
         59 . The method of  claim 58 , wherein the Fontan patient is at least 12 years old. 
     
     
         60 . The method of  claim 58 , wherein the Fontan patient is a female. 
     
     
         61 . The method of  claim 59 , wherein the Fontan patient is a female. 
     
     
         62 . The method of  claim 58 , wherein the Fontan patient is a male. 
     
     
         63 . The method of  claim 59 , wherein the Fontan patient is a male. 
     
     
         64 . The method of  claim 58 , wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage form. 
     
     
         65 . The method of  claim 64 , wherein the oral dosage form is a tablet. 
     
     
         66 . The method of  claim 64 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         67 . Use of an effective dose of udenafil, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of a human patient, who has undergone Fontan palliation for improving the human patient's exercise capacity, wherein the human patient's exercise capacity is adversely affected due to a decline in the human patient's myocardial function after the Fontan palliation, wherein the human patient is in need of treatment to improve the human patient's exercise capacity, and wherein the medicament is formulated for administration with an effective dose of udenafil, or a pharmaceutically acceptable salt thereof. 
     
     
         68 . The use of  claim 67 , wherein the effective dose of udenafil, or a pharmaceutically acceptable salt thereof, is about 87.5 mg, and wherein the medicament is formulated as an oral dosage. 
     
     
         69 . The use of  claim 67 , wherein the effective dose of udenafil, or a pharmaceutically acceptable salt thereof, is in a range of between about 87.5 mg and about 175 mg, and wherein the medicament is formulated as an oral dosage. 
     
     
         70 . The use of  claim 67 , wherein the human patient has single ventricle heart disease. 
     
     
         71 . The use of  claim 67 , wherein the human patient has single ventricle heart disease, and wherein the medicament is formulated as an oral dosage form. 
     
     
         72 . The use of  claim 68 , wherein the oral dosage form is a tablet. 
     
     
         73 . The use of  claim 69 , wherein the oral dosage form is a tablet. 
     
     
         74 . The use of  claim 71 , wherein the oral dosage form is a tablet. 
     
     
         75 . The use of  claim 68 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         76 . The use of  claim 69 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         77 . The use of  claim 71 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         78 . The use of  claim 67 , wherein the human patient is a female patient. 
     
     
         79 . The use of  claim 67 , wherein the human patient is a male patient. 
     
     
         80 . Use of an effective dose of udenafil, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treat of a human patient, who has undergone Fontan palliation, for improving the human patient's exercise capacity, whose exercise capacity is adversely affected due to a decline in the human patient's heart function after Fontan palliation, wherein the human patient is in need of treatment to improve the human patient's exercise capacity as determined by maximum oxygen uptake a maximum exercise output (VO 2  measurement), and wherein the medicament is formulated for administration of a total daily dose of udenafil, or a pharmaceutically acceptable salt thereof, from about 125 mg to about 175 mg. 
     
     
         81 . The use of  claim 80 , wherein the effective dose of udenafil, or a pharmaceutically acceptable salt thereof, is about 87.5 mg, and wherein the medicament is formulated as an oral dosage form for twice daily administration. 
     
     
         82 . The use of  claim 81 , wherein the human patient has single ventricle heart disease. 
     
     
         83 . The use of  claim 82 , wherein the human patient is at least about 12 years old. 
     
     
         84 . The use of  claim 81 , wherein the oral dosage form is a tablet. 
     
     
         85 . The use of  claim 81 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         86 . The use of  claim 82 , wherein the oral dosage form is a tablet. 
     
     
         87 . The use of  claim 82 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         88 . The use of  claim 80 , wherein the human patient has single ventricle heart disease. 
     
     
         89 . The use of  claim 86 , wherein the medicament is an oral dosage form. 
     
     
         90 . The use of  claim 87 , wherein the oral dosage form is a tablet. 
     
     
         91 . The use of  claim 87 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         92 . The use of  claim 88 , wherein the human patient is at least about 12 years old. 
     
     
         93 . The use of  claim 92 , wherein the medicament is an oral dosage form. 
     
     
         94 . The use of  claim 92 , wherein the oral dosage form is a tablet. 
     
     
         95 . The use of  claim 92 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         96 . The use of  claim 80 , wherein the human patient is at least about 12 years old. 
     
     
         97 . The use of  claim 96 , wherein the medicament is an oral dosage form. 
     
     
         98 . The use of  claim 97 , wherein the oral dosage form is a tablet. 
     
     
         99 . The use of  claim 97 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         100 . The use of  claim 80 , wherein the medicament is formulated as an oral dosage form. 
     
     
         101 . The use of  claim 100 , wherein the oral dosage form is a tablet. 
     
     
         102 . The use of  claim 100 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         103 . The use  claim 80 , wherein the human patient is a female. 
     
     
         104 . The use  claim 80 , wherein the human patient is a male. 
     
     
         105 . A method of treating a single ventricle heart disease (SVHD) patient with udenafil, or a pharmaceutically acceptable salt thereof, wherein the SVHD patient has undergone Fontan palliation and whose exercise capacity has been adversely affected due to a decline in the SVHD patient's myocardial function after the Fontan palliation, and wherein the SVHD patient is in need of treatment to improve the SVHD patient's exercise capacity, said method comprising:
 administering to the SVHD patient and whose exercise capacity has been adversely affected due to a decline in the SVHD patient's myocardial function after the Fontan palliation with an effective daily dose of udenafil, or a pharmaceutically acceptable salt thereof, to treat the SVHD patient.   
     
     
         106 . The method of  claim 105 , wherein the effective dose of udenafil, or a pharmaceutically acceptable salt thereof, is about 87.5 mg, and wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage. 
     
     
         107 . The method of  claim 105 , wherein the effective dose of udenafil, or a pharmaceutically acceptable salt thereof, is about 125 mg, and wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage. 
     
     
         108 . The use of  claim 105 , wherein the effective dose of udenafil, or a pharmaceutically acceptable salt thereof, is in a range of between about 87.5 mg and about 175 mg, and wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage. 
     
     
         109 . The use of  claim 105 , wherein the SVHD patient was born with single ventricle heart disease, and wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage. 
     
     
         110 . The use of  claim 105 , wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage form. 
     
     
         111 . The method of  claim 106 , wherein the oral dosage form is a tablet. 
     
     
         112 . The method of  claim 107 , wherein the oral dosage form is a tablet. 
     
     
         113 . The method of  claim 108 , wherein the oral dosage form is a tablet. 
     
     
         114 . The method of  claim 109 , wherein the oral dosage form is a tablet. 
     
     
         115 . The method of  claim 110 , wherein the oral dosage form is a tablet. 
     
     
         116 . The method of  claim 106 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         117 . The method of  claim 107 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         118 . The method of  claim 108 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         119 . The method of  claim 109 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         120 . The method of  claim 110 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension. 
     
     
         121 . The use of  claim 106 , wherein the SVHD patient is a female SVHD patient. 
     
     
         122 . The use of  claim 106 , wherein the SVHD patient is a male SVHD patient. 
     
     
         123 . The use of  claim 107 , wherein the SVHD patient is a female SVHD patient. 
     
     
         124 . The use of  claim 107 , wherein the SVHD patient is a male SVHD patient. 
     
     
         125 . The use of  claim 108 , wherein the SVHD patient is a female SVHD patient. 
     
     
         126 . The use of  claim 108 , wherein the SVHD patient is a male SVHD patient. 
     
     
         127 . The use of  claim 109 , wherein the SVHD patient is a female SVHD patient. 
     
     
         128 . The use of  claim 109 , wherein the SVHD patient is a male SVHD patient. 
     
     
         129 . The use of  claim 110 , wherein the SVHD patient is a female SVHD patient. 
     
     
         130 . The use of  claim 110 , wherein the SVHD patient is a male SVHD patient. 
     
     
         131 . The use of  claim 111 , wherein the SVHD patient is a female SVHD patient. 
     
     
         132 . The use of  claim 111 , wherein the SVHD patient is a male SVHD patient. 
     
     
         133 . The use of  claim 112 , wherein the SVHD patient is a female SVHD patient. 
     
     
         134 . The use of  claim 112 , wherein the SVHD patient is a male SVHD patient. 
     
     
         135 . The use of  claim 113 , wherein the SVHD patient is a female SVHD patient. 
     
     
         136 . The use of  claim 113 , wherein the SVHD patient is a male SVHD patient. 
     
     
         137 . The use of  claim 114 , wherein the SVHD patient is a female SVHD patient. 
     
     
         138 . The use of  claim 114 , wherein the SVHD patient is a male SVHD patient. 
     
     
         139 . The use of  claim 115 , wherein the SVHD patient is a female SVHD patient. 
     
     
         140 . The use of  claim 115 , wherein the SVHD patient is a male SVHD patient. 
     
     
         141 . The use of  claim 116 , wherein the SVHD patient is a female SVHD patient. 
     
     
         142 . The use of  claim 116 , wherein the SVHD patient is a male SVHD patient. 
     
     
         143 . A method of treating a human patient who has had a Fontan procedure for improving the patient's exercise capacity, wherein the human patient is in need of treatment to improve the patient's exercise capacity, the method comprising
 administering to the human patient who has undergone the Fontan procedure an effective amount of udenafil, or a pharmaceutically acceptable salt thereof, to improve the patient's exercise capacity.   
     
     
         144 . The method of  claim 143 , wherein the human patient is at least 12 years old. 
     
     
         145 . The method of  claim 143 , wherein the human patient is a female. 
     
     
         146 . The method of  claim 143 , wherein the human patient is a male. 
     
     
         147 . The method of  claim 143 , wherein the udenafil, or a pharmaceutically acceptable salt thereof, is formulated as an oral dosage form. 
     
     
         148 . The method of  claim 147 , wherein the oral dosage form is a tablet. 
     
     
         149 . The method of  claim 147 , wherein the oral dosage form is a solid or semi-solid oral dosage form selected from a group of solid or semi-solid oral dosage forms consisting of a tablet, a capsule, a gel, a liquid dispersion, a pill, a powder, and a suspension.