METHODS OF TREATING HEPATIC ENCEPHALOPATHY

• US 20110035232A1
• Filed: 06/02/2010
• Published: 02/10/2011
• Est. Priority Date: 10/02/2008
• Status: Abandoned Application

• Current Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Original Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Inventors: Shaw, Audrey, Merchant, Kunal, Bortey, Enoch, Forbes, William
• Application Number:
  US12/792,658
• Publication Number:
  US 20110035232A1
• Time in Patent Office: Days
• US Class Current: 705/2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Treatment of hepatic encephalopathy using gastrointestinal specific antibiotics is disclosed. One example of a gastrointestinal specific antibiotic is rifaximin. The instant application also provides methods for determining if a subject has a neurological condition or hepatic encephalopathy by determining the critical flicker frequency and/or the venous ammonia level of the subject at two or more time points. The further provided are methods for treating these subjects.

Claims

1. A method of decreasing blood ammonia levels in a subject comprising:

administering to the subject an effective amount of rifaximin, thereby reducing ammonia blood levels.

2-4. -4. (canceled)

5. A method of decreasing fatigue in a subject having hepatic encephalopathy comprising:

administering to the subject an effective amount of rifaximin, thereby reducing fatigue in a subject.

6. A method for treating a subject having HE, comprising:

administering a GI specific antibiotic with lactulose, thereby treating a subject having HE.

9. The method of claim 6, further comprising advising a health care worker to administer the GI specific antibiotic prior to, with, or after administration of lactulose.

15. The method of claim 6 wherein the GI specific antibiotic is rifaximin.

7. (canceled)

8. (canceled)

10-14. -14. (canceled)

16. A method of diagnosing hepatic encephalopathy (HE) in a subject comprising:

determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has hepatic encephalopathy.

17. The method of claim 16, wherein the CFF comprises the CFF time weighted average.

18. The method of claim 17, wherein the CFF time weighted average comprises less than about 24 Hz.

32. The method of claim 16, wherein the risk is increased as compared to a control subject without HE.

33. The method of claim 16, wherein the two or more time points occur within one week.

34. The method of claim 16, wherein the two or more time points occur within four weeks.

35. The method of claim 16, wherein the two or more time points occur within six months or more.

19. A method of determining a subject'"'"'s risk of an HE breakthrough event, comprising:

determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has an increased risk of an HE breakthrough event.

20. The method of claim 19, wherein the CFF comprises the CFF time weighted average.

21. The method of claim 20, wherein the CFF time weighted average comprises less than about 24 Hz.

22. The method of claim 19, wherein a average CFF time weighted average 10 Hz is indicative that the subject has the greatest risk of a HE breakthrough event.

23. A method of determining the prognosis of a subject having HE, comprising:

determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has a poor prognosis.

24. The method of claim 23, wherein the CFF is the CFF time weighted average.

25. The method of claim 24, wherein the CFF time weighted average comprises less than about 24 Hz.

26. The method of claim 24, wherein the CFF time weighted average comprises less than about 20 Hz.

27. A method of treating or preventing an HE event, comprising:

determining the critical flicker frequency (CFF) of a subject at two or more time points,

administering to a subject having a decrease in the CFF average between the time points an effective amount of a GI specific antibiotic,

thereby treating or preventing an HE event.

28. The method of claim 27, wherein the CFF comprises the CFF time weighted average.

29. The method of claim 28, wherein the CFF time weighted average comprises less than about 24 Hz.

30. The method of claim 28, wherein the subject is administered a GI specific antibiotic when the CFF time weighted average comprises less than 24 Hz.

31. The method of claim 30, wherein the GI specific antibiotic is rifaximin.

36. A method of diagnosing hepatic encephalopathy (HE) in a subject comprising:

determining the venous ammonia levels of a subject at two or more time points, wherein an increase in the venous ammonia levels is indicative that the subject has hepatic encephalopathy.

37. The method of claim 36, wherein the venous ammonia level comprises the time weighted average venous ammonia levels.

38. The method of claim 37, wherein the time weighted average venous ammonia level comprises more than about 100 μ

mol/L.

50. The method of claim 36, wherein the two or more time points occur within one week.

51. The method of claim 36, wherein the two or more time points occur within four weeks.

52. The method of claim 36, wherein the two or more time points occur within six months or more.

39-44. -44. (canceled)

45. A method of treating or preventing an HE event, comprising:

determining the venous ammonia level of a subject at two or more time points,

administering to a subject having an increase in the venous ammonia level between the time points an effective amount of a GI specific antibiotic,

thereby treating or preventing an HE event.

46. The method of claim 45, wherein the GI specific antibiotic is rifaximin.

47. The method of claim 46, wherein the venous ammonia level comprises the time weighted average venous ammonia levels.

48. The method of claim 47, wherein the time weighted average venous ammonia level is more than about 100 μ

mol/L.

49. The method of claim 45, further comprising administering lactulose.

53-57. -57. (canceled)

58. A method of diagnosing a neurological disease in a subject, comprising:

determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has a neurological disease.

60. The method of claim 58, wherein the neurological disease or disorder is Alzheimer'"'"'s disease, Parkinson'"'"'s disease, brain trauma, migraine, chronic headache, insomnia and other sleep disorders, and/or epilepsy.

59. (canceled)

61. A method of determining the prognosis of a subject having a neurological disease, comprising:

determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has a poor prognosis.

62. The method of claim 61, wherein the CFF is the CFF time weighted average.

63. The method of claim 61, wherein the neurological disease or disorder is Alzheimer'"'"'s disease or Parkinson'"'"'s disease.

64-66. -66. (canceled)

67. A computerized method for identifying subjects having a neurological disease comprising:

maintaining a database of CFFs for subjects at various time points and stages of disease progression;

comparing the results of an individuals CFF results taken at two or more time points to the database;

obtaining the diagnosis of a neurological disease from the computer if subject has CFF results that decrease between measurements.

68. The method of claim 67, wherein the CFF comprises the CFF time weighted average.

70. The method of claim 67, further comprising controlling a printing device to print a report based on the results of the method.

69. (canceled)

71. A business method for decreasing healthcare costs comprising:

determining the critical flicker frequency (CFF) of a subject at two or more time points;

storing patient information on a computer processor;

determining if the subject has a neurological disease by determining if the CFF value has decreased between time points; and

treating the subject as necessary to avoid or delay hospitalization.

72. (canceled)

73. A device for determining the risk of an HE event, comprising:

a flicker box, a measurement device to determine CFF, and a computer with an algorithm.

74. (canceled)