Method of treating the syndrome of lipodystrophy

1. A method of treating a human suffering from the Syndrome of Lipodystrophy or one or more HIV-related abnormalities included therein, the method comprising:

administering, by a pharmaceutically effective mode, a drug composition comprising an opioidergic composition.

2. The method of claim 1 , wherein the opioidergic composition includes at least one of an opiate antagonist, an opiate agonist and a combination thereof.

3. The method of claim 2 , wherein the opiate antagonist comprises a single molecular entity.

4. The method of claim 2 , wherein the opiate antagonist comprises a combination of molecular entities.

5. The method of claim 2 , wherein the drug composition comprises an opiate antagonist and the opiate antagonist has drug opiate antagonist IC 50 values, and the IC 50 values for the μ, δ and κ opiate receptors have ratios such that:

{(IC 50 κ/IC 50 μ)<10}, and {(IC 50 κ/IC 50 δ)<10}.

6. The method of claim 2 , wherein the opiate agonist comprises a single molecular entity.

7. The method of claim 2 , wherein the opiate agonist comprises a combination of molecular entities.

8. The method of claim 1 , wherein the opioidergic composition comprises a peripherally-acting μ-agonist.

9. The method of claim 8 , wherein the opioidergic composition comprises loperamide.

10. The method of claim 1 , wherein the opioidergic composition comprises a centrally-acting μ-agonist.

11. The method of claim 1 , wherein the opioidergic composition comprises an opiate having mixed μ-agonist and κ antagonist activity.

12. The method of claim 11 , wherein the opiate having mixed μ-agonist and κ antagonist activity is buprenorphine.

13. The method of claim 1 wherein the opioidergic composition includes at least one of the following:

i) dihydromorphine;

ii) morphine;

iii) hydromorphone;

iv) methadone;

v) fentanyl;

vi) sufentanyl;

vii) buprenorphine;

viii) demorphine;

ix) codeine;

x) ethylmorphine;

xi) etonitazene;

xii) hydrocodone;

xiii) levorphanol;

xiv) norcodeine;

xv) normorphine;

xvi) (D—Ala 2 —N—Me—Phe 4 —Gly 3 —ol)-Enkephalin (DAMGO);

xvii) oxycodone; and

xviii) tramadol.

14. The method of claim 1 , wherein the opioidergic composition includes at least one of the following:

i) nalmefene;

ii) naltrexone;

iii) nor-binaltorphimine;

iv) (−)-(1R,5R,9R)-5,9-diethyl-2-(3-furylmethyl)-2-hydroxy-6,7-benzomorphan (MR 2266);

v) a triethylenedioxy derivative of B-naltrexamine (TENA); and

vi) guanidylated naltrindole (GNTI).

15. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is atherogenic dyslipidemia (AD).

16. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is hypertriglyceridemia (HTG).

17. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is elevated levels of cholesterol (Chol).

18. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is elevated levels of low-density-lipoprotein cholesterol (LDL).

19. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is low levels of high-density lipoprotein cholesterol (HDL).

20. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is insulin resistance (IR).

21. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is beta-cell dysfunction.

22. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is the loss of first phase insulin secretion.

23. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is impaired glucose tolerance (IGT).

24. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is Type 2 Diabetes.

25. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is elevated endogenous glucose production.

26. The method of claim 1 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is excessive gluconeogenesis.

27. The method of claim 1 , further comprising a pre-treatment regimen comprising the daily administration of nalmefene in the range of 1-10 mg for a period of up to 6 weeks.

28. A method of treating a human suffering from the Syndrome of Lipodystrophy or one or more HIV-related abnormalities included therein, the method comprising:

administering, by a pharmaceutically effective mode, a drug composition comprising an opioidergic composition and at least one insulin secretagogue.

29. The method of claim 28 , wherein the insulin secretagogue includes at least one of the following:

i. sulphonylureas;

ii. tolbutamide;

iii. chlorpropamide;

iv. glimepiride;

v. glipizide;

vi. glyburide;

vii. meglitinides;

viii. repaglinide;

ix. pramlintide;

x. morphilinoguanide;

xi. acetylcholine;

xii. muscarinic agonists;

xiii. carbachol;

xiv. bethanechol;

xv. beta-L-glucose pentaacetate;

xvi. chiro-inositol;

xvii. myo-inositol;

xviii. GIP;

xix. GLP-1; and

xx. Extendin-4.

30. The method of claim 28 , wherein the insulin secretagogue is a non-glucose dependent insulin secretagogue, the method producing insulin release patterns capable of attaining glucose dependent, bi-phasic release characteristics with reduced likelihood of producing hypoglycemia.

31. The method of claim 28 , wherein the insulin secretagogue comprises sulphonylurea.

32. The method of claim 28 , wherein the opioidergic composition includes at least one of an opiate antagonist, an opiate agonist and a combination thereof.

33. The method of claim 28 , wherein the opiate antagonist comprises a single molecular entity.

34. The method of claim 28 , wherein the opiate antagonist comprises a combination of molecular entities.

35. The method of claim 28 , wherein the opioidergic composition includes at least one of the following:

i) dihydromorphine;

ii) morphine;

iii) hydromorphone;

iv) methadone;

v) fentanyl;

vi) sufentanyl;

vii) demorphine;

viii) codeine;

ix) ethylmorphine;

x) etonitazene;

xi) hydrocodone;

xii) levorphanol;

xiii) norcodeine;

xiv) normorphine;

xv) (D—Ala 2 —N—Me—Phe 4 —Gly 3 —ol) -Enkephalin (DAMGO);

xvi) oxycodone; and

xvii) tramadol.

36. The method of claim 28 , wherein the opioidergic composition includes at least one of the following:

i) nalmefene ii) naltrexone;

iii) nor-binaltorphimine;

iv) (−)-(1R,5R,9R)-5,9-diethyl-2-(3-furylmethyl)-2-hydroxy-6,7-benzomorphan (MR 2266);

v) a triethylenedioxy derivative of B-naltrexamine (TENA); and

vi) guanidylated naltrindole (GNTI).

37. The method of claim 28 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy includes at least one of atherogenic dyslipidemia (AD), hypertriglyceridemia (HTG), elevated levels of cholesterol (Chol), elevated levels of low-density-lipoprotein cholesterol (LDL), low levels of high-density lipoprotein cholesterol (HDL), insulin resistance (IR), beta-cell dysfunction, impaired or loss of first phase insulin secretion, impaired glucose tolerance (IGT), Type 2 Diabetes, elevated endogenous glucose production, and excessive gluconeogenesis.

38. The method of claim 28 , wherein the drug composition is a single agent having opioidergic activity and insulinotropic activity.

39. A method of treating a human suffering from the Syndrome of Lipodystrophy or one or more HIV-related abnormalities included therein, the method comprising:

administering, by a pharmaceutically effective mode, a drug composition comprising

at least one opiate agonist; and

at least one opiate antagonist.

40. The method of claim 39 , wherein the drug composition further comprises at least one insulin secretagogue.

41. The method of claim 39 , wherein the insulin secretagogue includes at least one of the following:

i. sulphonylureas;

ii. tolbutamide;

iii. chlorpropamide;

iv. glimepiride;

v. glipizide;

vi. glyburide;

vii. meglitinides;

viii. repaglinide;

ix. pramlintide;

x. morphilinoguanide;

xi. acetylcholine;

xii. muscarinic agonists;

xiii. carbachol;

xiv. bethanechol;

xv. beta-L-glucose pentaacetate;

xvi. chiro-inositol;

xvii. myo-inositol;

xviii. GIP;

xix. GLP-1; and

xx. Extendin-4.

42. The method of claim 40 , wherein the insulin secretagogue is a non-glucose dependent insulin secretagogue, the method producing insulin release patterns capable of attaining glucose dependent, bi-phasic release characteristics with reduced likelihood of producing hypoglycemia.

43. The method of claim 40 , wherein the insulin secretagogue includes sulphonylurea.

44. The method of claim 39 , wherein the opiate agonist includes a μ-agonist.

45. The method of claim 39 , wherein the opiate agonist includes loperamide.

46. The method of claim 39 , wherein the opiate agonist includes at least one of a centrally-acting μ agonist and a peripherally-acting μ agonist.

47. The method of claim 39 , wherein the opiate agonist includes at least one of the following:

xviii) dihydromorphine;

xix) morphine;

xx) hydromorphone;

xxi) methadone;

xxii) fentanyl;

xxiii) sufentanyl;

xxiv) demorphine;

xxv) codeine;

xxvi) ethylmorphine;

xxvii) etonitazene;

xxviii) hydrocodone;

xxix) levorphanol;

xxx) norcodeine;

xxxi) normorphine;

xxxii) (D—Ala 2 —N—Me—Phe 4 —Gly 3 —ol)-Enkephalin (DAMGO);

xxxiii) oxycodone; and

xxxiv) tramadol.

48. The method of claim 39 , wherein the HIV-related abnormality included in the Syndrome of Lipodystrophy is at least one of atherogenic dyslipidemia (AD), hypertriglyceridemia (HTG), elevated levels of cholesterol (Chol), elevated levels of low-density-lipoprotein cholesterol (LDL), low levels of high-density lipoprotein cholesterol (HDL), insulin resistance (IR), beta-cell dysfunction, impaired or loss of first phase insulin secretion, impaired glucose tolerance (IGT), Type 2 Diabetes, elevated endogenous glucose production, and excessive gluconeogenesis.