Claims
- 1. A method for determining the initial dose to administer to a human subject of a semisolid topical composition having a pH value of between about 4 to about 8 and comprising 0.1% to about 2% w/w of a human sex hormone, a penetration-enhancing amount of oleic acid; a C1-C4 alcohol; and a glycol, said method comprising:
determining the body weight of the subject; selecting the dose according to a predetermined empirical relationship between the body weight, the applied dosage, and the serum level of the hormone in a reference population at steady state.
- 2. The method of claim 1, wherein the relationship is between BMI, the applied dosage, and the Cavg serum level of the hormone.
- 3. The method of claim 1, wherein the hormone is testosterone.
- 4. The method of claim 1, wherein the hormone is estrogen.
- 5 The method of claim 1, wherein the serum level is Cmin.
- 6. The method of claim 1, wherein if the subject has a BMI less than 18.5, the initial dose is 2 g gel; if the subject has a BMI is between 18.5 and 35, the initial dose is 3 g gel; or if the subject has a BMI greater than 35, the initial dose is 4 g gel.
- 7. A method for determining the dose to administer to a human subject of a semisolid topical composition comprising a therapeutic amount of a mammalian hormone and an effective amount of a penetration enhancer, said method comprising:
determining the weight and height of the subject; calculating the Body Mass Index (BMI) of the subject; and adjusting the dose according to the BMI.
- 8. The method of claim 7 wherein the adjusting is based upon a predetermined empirical relationship between BMI, the amount of the composition applied, and the serum hormone concentration level measured in a reference population at steady state.
- 9. The method of claim 7, wherein the hormone is a human sex hormone.
- 10. The method of claim 7, wherein the hormone is an androgen.
- 11. The method of claim 9, wherein the hormone is an estrogen.
- 12. The method of claim 10, wherein the hormone is testosterone or a salt or ester thereof.
- 13. The method of claim 11, wherein the hormone is a pharmaceutically acceptable salt or ester of estrogen or estradiol.
- 14. The method of claim 7, wherein the hormone is a progestin.
- 15. The method of claim 14, wherein the hormone is progesterone or a salt or ester of progesterone.
- 16. The method of claim 7, wherein the enhancer is oleic acid.
- 17. The method of claim 7, wherein the hormone has a steroid moeity.
- 18. The method of claim 7, wherein the topical composition has a pH value of between about 4 to about 8 and comprises
a) the hormone in a concentration of about 0.1% to about 2% w/w, and b) a penetration-enhancing system consisting essentially of (i) a membrane fluidizer comprising oleic acid; (ii) a C1-C4 alcohol; and (iii) a glycol.
- 19. The method of claim 17, wherein the hormone is a member selected from the group consisting of testosterone, estradiol, progestin, and derivatives and mixtures thereof.
- 20. The method of claim 18, wherein the penetration-enhancing system further comprises (iv) a gelling agent.
- 21. The method of claim 10, wherein the subject is a male with primary or secondary hypogonadism, male sexual desire disorder, male sexual arousal disorder, AIDS, wasting syndrome associated with chronic illnesses, end stage renal disease, chronic fatigue syndrome, Epstein-Barr virus, heart disease, cancer, diabetes, Alzheimer's disease, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, or osteoporosis.
- 22. The method of claim 7, wherein the subject is a female with sexual dysfunction or with a reduced feeling of well-being, AIDS, wasting syndrome associated with chronic illnesses, end stage renal disease, chronic fatigue syndrome, Epstein-Barr virus, heart disease, cancer, diabetes, Alzheimer's disease, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, osteoporosis, or Turner's Syndrome.
- 23. The method of claim 8, wherein adjusting the dose increases the dose by an average of about 1-10% for each single unit increase in the BMI for subjects having a BMI value of 30 to 50 kg/m2.
- 24. The method of claim 10, wherein the subject is male and had a pretreatment average serum testosterone level below 300 ng/dl.
- 25. The method of claim 7, wherein the dose is an initial dose.
- 26. The method of claim 7, wherein said composition is selected from the group consisting of solutions, creams, lotions, ointments, and gels.
- 27. The method of claim 26, wherein said composition has a testosterone concentration of about 0.01% to about 5% w/w.
- 28. The method of claim 7, wherein the dose is a daily dosage.
- 29. A method of administering a therapeutically effective amount of a mammalian sex hormone to a human subject; said method comprising:
calculating a dose of a topical composition comprising the sex hormone and a penetration enhancer according to the method of claim 1; and administering the dose of the composition to the skin of the subject.
- 30. A method of restoring serum sex hormone levels in a human subject to normal levels, said method comprising:
determining the height and weight of the subject; using the height and weight of the subject to estimate a first dose amount of a topical composition comprising the sex hormone and a penetration enhancer; applying at least daily to the skin of the subject the composition in the first dose amount; measuring the level of the sex hormone in the blood of the subject; and if the blood sex hormone level is below a first predetermined level, treating the subject with a second dose 25 to 100% greater than the first dose amount; or, if the blood sex hormone level is above or near a second predetermined level, treating the subject with a third dose which is 25 to 75% less than the first dose amount
- 31. The method of claim 30, wherein the sex hormone is an androgen selected from the group consisting of testosterone, its salts, esters, and derivatives.
- 32. The method of claim 31, wherein the testosterone is measured two hours after the initial daily application of the first dose amount.
- 33. The method of claim 31, wherein the testosterone is measured at the blood testosterone steady state.
- 34. The method of claim 30, wherein the testosterone is measured at least three days after the first application of the composition.
- 35. The method of claim 30, wherein the topical composition has a pH value of between about 4 to about 8, and comprises:
a) the hormone in a concentration of about 0.1% to about 2% w/w, and b) a penetration-enhancing system consisting essentially of (i) a membrane fluidizer comprising oleic acid; (ii) a C1-C4 alcohol; and (iii) a glycol.
- 36. The method of claim 30, wherein the sex hormone is an androgen or an estrogen.
- 37. The method of claim 33, wherein the first predetermined level is about 250-350 ng/dl and the second predetermined level is about 1000-1200 ng/dl.
- 38. A metered device for delivering a topical composition comprising testosterone and a penetration enhancer to a subject, wherein said metered device provides an identical amount of the composition on each administration and wherein the amount administered is determined by the BMI of the subject.
- 39. The kit comprising:
a pharmaceutical composition comprising a therapeutic amount of a mammalian hormone and an effective amount of a skin penetration enhancer; a metered dose pump holding said composition in an amount to provide more than one dose; said pump set to deliver a fixed amount of the pharmaceutical composition when the pump is activated.
- 40. The kit of claim 39 further comprising instructions on how to activate the pump.
- 41. The kit of claim 39 further comprising instructions on where to apply the composition to the skin.
- 42. A method for determining the dose to administer to a human subject of a semisolid topical composition comprising a therapeutic amount of a mammalian hormone and an effective amount of a penetration enhancer, said method comprising:
determining the body weight and height of the subject; and adjusting the dose according to the body weight.
- 43. The method of claim 42, wherein the adjusting is based upon a predetermined empirical relationship between body weight, the amount of the composition applied, and the serum hormone concentration level measured in a reference population at steady state.
- 44. A method of adjusting serum sex hormone levels in a human subject to normal levels, said method comprising:
determining the weight of the subject; using the weight of the subject to establish a first dose amount of a topical composition comprising the sex hormone and a penetration enhancer wherein the establishing is based upon a predetermined empirical relationship between body weight, the amount of the composition applied, and the serum hormone concentration level measured in a reference population at steady state; applying at least daily to the skin of the subject the composition in the first dose amount; measuring the level of the sex hormone in the blood of the subject; and if the blood sex hormone level is below a first predetermined level treating the subject with a second dose 25 to 100% greater than the first dose amount; or if the blood sex hormone level is above or near a second predetermined level, treating the subject with a third dose which is 25 to 75% less than the first dose amount.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from U.S. Patent Application No.60/327,423 filed Oct. 4, 2001 which is incorporated by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60327423 |
Oct 2001 |
US |