ORAL TESTOSTERONE ESTER FORMULATIONS AND METHODS OF TREATING TESTOSTERONE DEFICIENCY COMPRISING SAME
A pharmaceutical formulation of testosterone undecanoate is provided. Methods of treating a testosterone deficiency or its symptoms with the inventive formulations are also provided.
1 . An oral pharmaceutical composition comprising testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon once- or twice-daily oral administration, provides an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL.
2 . The pharmaceutical composition of claim 1 , which provides a C max that does not exceed 2500 ng/dL when administered with a meal.
3 . The pharmaceutical composition of claim 1 , which provides a C max that does not exceed 1800 ng/dL when administered with a meal.
4 . The pharmaceutical composition of claim 1 , which provides a C max that does not exceed 1500 ng/dL when administered with a meal.
5 . The oral pharmaceutical composition of claim 1 in which the at least one hydrophilic surfactant comprises Cremophor RH 40 (polyoxyethyleneglycerol trihydroxystearate).
6 . The oral pharmaceutical composition of claim 1 in which the at least one lipophilic surfactant comprises oleic acid.
7 . The oral pharmaceutical composition of claim 1 comprising 18 to 22 percent by weight of a solubilized testosterone undecanoate.
8 . The oral pharmaceutical composition of claim 7 in which the testosterone undecanoate is solubilized in a carrier substantially free of ethanol.
9 - 15 . (canceled)
16 . A pharmaceutical composition comprising testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon once- or twice-daily oral administration to a subject suffering from testosterone deficiency or its symptoms, provides a mean serum testosterone concentration at day 30 of a daily treatment regimen, which is substantially the same as that observed on day 7.
17 . The pharmaceutical composition of claim 16 in which the mean serum testosterone concentration obtained at day 30 of a daily treatment regimen is substantially the same as that observed on day 60.
18 . A method of treating testosterone deficiency or its symptoms comprising orally administering to a subject suffering from testosterone deficiency or its symptoms an effective amount of a pharmaceutical composition comprising testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1 to provide an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL.
19 . (canceled)
20 . The method of claim 18 in which the composition is administered twice daily.
21 . The method of claim 18 which gives rise to a C max value falling in the range of about 900 to 1100 ng/dL
22 . The method of claim 18 in which the composition is administered with a meal comprising at least 20 wt % fat.
23 . The method of claim 18 which gives rise to substantially no diurnal testosterone pharmacokinetic variation.
24 . The method of claim 18 which gives rise to an average serum T max value falling in the range of about 3 to 7 hours after oral administration.
25 . (canceled)
26 . The method of claim 18 in which substantially no significant decline in steady state serum testosterone response is observed upon repeat dosing.