COMPOSITIONS AND METHODS OF USING MODIFIED RELEASE SOLABEGRON FOR LOWER URINARY TRACT SYMPTOMS
This application relates to pharmaceutical compositions, comprising solabegron that are useful for the treatment of lower urinary tract symptoms such as, for example, overactive bladder and prostate disorders. Additionally, this application relates to methods for treating lower urinary tract symptoms utilizing the pharmaceutical compositions, comprising solabegron. In some embodiments, the pharmaceutical compositions, comprising solabegron comprise a dual release drug delivery system.
1 - 52 . (canceled)
53 . A method of treating overactive bladder in a patient in need thereof comprising:
orally administering simultaneously once a day to the patient a pharmaceutical composition, wherein the pharmaceutical composition comprises
an immediate release composition comprising about 75 mg to about 250 mg of solabegron and at least one pharmaceutically acceptable carrier or diluent, and
a delayed release composition comprising about 100 mg to about 300 mg of solabegron and at least one pharmaceutically acceptable carrier or diluent,
wherein the pharmaceutical composition achieves a first target C max of about 0.5 μg/ml to about 4 μg/ml, a second target C max of about 0.5 μg/ml to about 4 μg/ml, and a target AUC of solabegron of about 11,000 ng·hr/ml to about 30,000 ng·hr/ml over a twenty-four hour period after administration.
54 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max in about 0.75 hours to about 4 hours after administration, and the second target C max in about 6 hours to about 16 hours after administration.
55 . The method of claim 53 , wherein the pharmaceutical composition achieves a first C min concentration of about 0.25 μg/ml to about 1.5 μg/ml between the first target C max and the second target C max .
56 . The method of claim 53 , wherein the pharmaceutical composition achieves a second C min concentration of about 0.01 μg/ml to about 1.0 μg/ml after the second target C max .
57 . The method of claim 55 , wherein the pharmaceutical composition achieves the first C min concentration in about 4 hours to about 8 hours after administration.
58 . The method of claim 56 , wherein the pharmaceutical composition achieves the second C min concentration about 24 hours after administration.
59 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max of about 1.5 μg/ml to about 4 μg/ml.
60 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max of about 1 μg/ml to about 3.5 μg/ml.
61 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max of about 1 μg/ml to about 2 μg/ml.
62 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max of about 1.5 μg/ml to about 3.5 μg/ml.
63 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max of about 1 μg/ml to about 3.0 μg/ml.
64 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max of about 2 μg/ml to about 3.5 μg/ml.
65 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max of about 2 μg/ml to about 3 μg/ml.
66 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max of about 0.5 μg/ml to about 3.5 μg/ml.
67 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max of about 1.5 μg/ml to about 4 μg/ml.
68 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max of about 1.5 μg/ml to about 3 μg/ml.
69 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max of about 2.5 μg/ml to about 4 μg/ml.
70 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max of about 2 μg/ml to about 4 μg/ml.
71 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max of about 2 μg/ml to about 3 μg/ml.
72 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max of about 3 μg/ml to about 4 μg/ml.
73 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max in about 1.5 hours to about 3 hours after administration.
74 . The method of claim 53 , wherein the pharmaceutical composition achieves the first target C max in about 1 hour to about 3 hours after administration.
75 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max in about 12 hours to about 20 hours after administration.
76 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max in about 14 hours to about 16 hours after administration.
77 . The method of claim 53 , wherein the pharmaceutical composition achieves the second target C max in about 5 hours to about 11 hours after administration.
78 . The method of claim 55 , wherein the pharmaceutical composition achieves the second target C max in about 2 hours to about 8 hours after the first C min .
79 . The method of claim 55 , wherein the pharmaceutical composition achieves the second target C max in about 4 hours to about 6 hours after the first C min .
80 . The method of claim 53 , wherein time between the first target C max and the second target C max is about 2 hours to about 8 hours.
81 . The method of claim 53 , wherein time between the first target C max and the second target C max is about 3 hours to about 7 hours.
82 . The method of claim 53 , wherein time between the first target C max and the second target C max is about 4 hours to about 6 hours.
83 . The method of claim 55 , wherein the pharmaceutical composition achieves the first C min concentration of about 0.25 μg/ml to about 1.0 μg/ml.
84 . The method of claim 55 , wherein the pharmaceutical composition achieves the first C min concentration of about 0.5 μg/ml to about 1.5 μg/ml.
85 . The method of claim 55 , wherein the pharmaceutical composition achieves the first C min concentration of about 0.5 μg/ml to about 1.0 μg/ml.
86 . The method of claim 55 , wherein the pharmaceutical composition achieves the first C min concentration of about 0.75 μg/ml to about 1.5 μg/ml.
87 . The method of claim 55 , wherein the pharmaceutical composition achieves the first C min concentration of about 0.25 μg/ml to about 1.25 μg/ml.
88 . The method of claim 56 , wherein the pharmaceutical composition achieves the second C min concentration of about 0.1 μg/ml to about 1 μg/ml.
89 . The method of claim 56 , wherein the pharmaceutical composition achieves the second C min concentration of about 0.25 μg/ml to about 1 μg/ml.
90 . The method of claim 56 , wherein the pharmaceutical composition achieves the second C min concentration of about 0.5 μg/ml to about 1 μg/ml.
91 . The method of claim 56 , wherein the pharmaceutical composition achieves the second C min concentration of about 0.75 μg/ml to about 1 μg/ml.
92 . The method of claim 56 , wherein the pharmaceutical composition achieves the second C min concentration of about 0.01 μg/ml to about 0.5 μg/ml.
93 . The method of claim 57 , wherein the pharmaceutical composition achieves the first C min concentration in about 5 hours to about 6 hours after administration.
94 . The method of claim 57 , wherein the pharmaceutical composition achieves the first C min concentration in about 3 hours to about 5 hours after administration.
95 . The method of claim 58 , wherein the pharmaceutical composition achieves the second C min concentration before about 20 hours after administration.
96 . The method of claim 58 , wherein the pharmaceutical composition achieves the second C min concentration before about 16 hours after administration.
97 . The method of claim 53 , wherein the pharmaceutical composition is a tablet, a bi-layer tablet, a capsule, a multiparticulate, a drug coated sphere, a matrix tablet, or a multicore tablet.
98 . The method of claim 53 , wherein the pharmaceutical composition is a single unit dose.
99 . The method of claim 53 , further comprising administering to the patient one more additional therapeutic agents selected from the groups consisting of antimuscarinic agents, alpha adrenoceptor blockers, botulinum toxin, purinergics, cannabinoids, transient receptor potential (TRP) protein inhibitors, prostaglandins, percutaneous tibial nerve stimulation, 5-alpha reductase inhibitors, phosphodiesterase-5 inhibitors, and combination thereof.
100 . The method of claim 99 , wherein the antimuscarinic agent is selected from the group consisting of tolterodine, oxybutynin, trospium, solifenacin, darifenacin, propiverine, fesoterodine, and pharmaceutically acceptable salts thereof, combinations thereof.
101 . The method of claim 53 , wherein
the immediate release composition comprises about 75 mg of solabegron and at least one pharmaceutically acceptable carrier or diluent,
the delayed release composition comprises about 200 mg of solabegron and at least one pharmaceutically acceptable carrier or diluent, and
wherein the pharmaceutical composition achieves the first target C max of about 1 μg/ml to about 2 μg/ml, and the second target C max of about 0.5 μg/ml to about 4 μg/ml.
102 . The method of claim 101 , wherein the pharmaceutical composition achieves the first target C max in about 0.75 hours to about 4 hours after administration, and the second target C max in about 5 hours to about 11 hours after administration.
103 . The method of claim 101 , wherein the pharmaceutical composition is a single unit dose.
104 . The method of claim 53 , wherein
the immediate release composition comprises about 125 mg of solabegron and at least one pharmaceutically acceptable carrier or diluent,
the delayed release composition comprises about 275 mg of solabegron and at least one pharmaceutically acceptable carrier or diluent, and
wherein the pharmaceutical composition achieves the first target C max of about 2 μg/ml to about 3 μg/ml, and the second target C max of about 0.5 μg/ml to about 4 μg/ml.
105 . The method of claim 104 , wherein the pharmaceutical composition achieves the first target C max in about 0.75 hours to about 4 hours after administration, and the second target C max in about 5 hours to about 11 hours after administration.
106 . The method of claim 104 , wherein the pharmaceutical composition is a single unit dose.