HIGH-STRENGTH TESTOSTERONE UNDECANOATE COMPOSITIONS
The present disclosure is drawn to pharmaceutical compositions and oral dosage capsules containing testosterone undecanoate, as well as related methods. The capsule includes a capsule shell and a capsule fill. The capsule fill can include a solubilizer and about 14 wt % to about 35 wt % testosterone undecanoate based on the total capsule fill. The oral dosage capsule is such that when a single oral administration to a male subject of one or more capsules with a total testosterone undecanoate daily dose of about 350 mg to about 650 mg it provides a ratio of serum testosterone C max to serum testosterone C ave of about 2.7 or less. In yet another embodiment, a method for providing a serum concentration of testosterone within a target serum testosterone concentration C ave range for a male subject is provided.
1 . A method for replacement therapy in a male having a condition associated with a deficiency or absence of endogenous testosterone said method comprising:
(a) orally administering to said male an initial daily dose dosing regimen of a pharmaceutical composition comprising about 14 weight % (wt %) to about 35 wt % testosterone undecanoate and a carrier, that provides from about 450 mg to about 480 mg of testosterone undecanoate to said male per day;
(b) determining a serum or plasma level of testosterone of said male during the daily dosing regimen at from 1-8 hours after single dose administration of said pharmaceutical composition at steady state; and
(c) orally administering a maintenance daily dose dosing regimen of a pharmaceutical composition comprising about 14 wt % to about 35 wt % testosterone undecanoate and a carrier, that provides within plus or minus 40% of the initial daily dose to said male per day to provide a serum or plasma testosterone C ave in said male in the eugonadal range.
2 . The method of claim 1 , further comprising:
(d) determining a serum or plasma level of testosterone of said male during the maintenance daily dosing regimen at from 1-8 hours after single dose administration of said pharmaceutical composition at steady state; and
(e) orally administering a second maintenance daily dose dosing regimen of a pharmaceutical composition comprising about 14 wt % to about 35 wt % testosterone undecanoate and a carrier, that provides within plus or minus 40% of the maintenance daily dose to said male per day.
3 . The method of claim 1 , wherein said orally administering provides about 480 mg of testosterone undecanoate per day.
4 . The method of claim 1 , wherein in said orally administering is twice a day administration.
5 . The method of claim 1 , wherein in said carrier comprises one or more of: a fatty acid, a monoglyceride, a diglyceride, a triglyceride and a hydrophilic surfactant.
6 . The method of claim 1 , wherein in said carrier comprises a fatty acid, a triglyceride and a hydrophilic surfactant.
7 . The method of claim 1 , wherein in said carrier comprises a fatty acid, a triglyceride and polyoxyl 40 hydrogenated castor oil.
8 . The method of claim 1 , wherein in said carrier comprises a fatty acid, borage oil and a hydrophilic surfactant.
9 . The method of claim 1 wherein in said carrier comprises oleic acid, a triglyceride and a hydrophilic surfactant.
10 . The method of claim 1 , wherein said carrier comprises a fatty acid, a triglyceride, an alcohol and a hydrophilic surfactant.
11 . The method of claim 1 , wherein said carrier comprises a fatty acid, a triglyceride, a vegetable oil and a hydrophilic surfactant.
12 . The method of claim 1 , wherein said carrier comprises oleic acid, borage oil, a vegetable oil and polyoxyl 40 hydrogenated castor oil.
13 . The method of claim 1 , wherein the method provides a steady state plasma or serum testosterone C ave of from 350 ng/dL to 800 ng/dL.
14 . The method of claim 1 , wherein said determining the serum or plasma level of testosterone of said male during the daily dosing regimen is at from 3-6 hours after single dose administration of said pharmaceutical composition at steady state.
15 . The method of claim 2 , wherein said determining the serum or plasma level of testosterone of said male during the maintenance daily dosing regimen is at from 3-6 hours after single dose administration of said pharmaceutical composition at steady state.