Methods of treating traveler's diarrhea and hepatic encephalopathy

• US 8,829,017 B2
• Filed: 03/31/2011
• Issued: 09/09/2014
• Est. Priority Date: 10/02/2008
• Status: Active Grant

• Current Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Original Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Inventors: Forbes, William, Bortey, Enoch
• Primary Examiner(s): Hui, San-Ming
• Assistant Examiner(s): CRUZ, KATHRIEN ANN
• Application Number:
  US13/076,967
• Publication Number:
  US 20110178113A1
• Time in Patent Office: 1,258 Days
• Field of Search: 514/279
• US Class Current: 514/279
• 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: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Treatment of traveler'"'"'s diarrhea using in subjects having hepatic encephalopathy using gastrointestinal specific antibiotics is disclosed. One example of a gastrointestinal specific antibiotic is rifaximin.

Claims

1. A method of treating a patient having hepatic encephalopathy (HE) comprising:

identifying a subject having Travelers'"'"' Diarrhea (TD) that also has hepatic insufficiency;

determining if the subject'"'"'s Child-Pugh score is Child-Pugh Class C or if the subject'"'"'s model end stage liver disease (MELD) score is 25 or greater; and

administering between 1000 and 1200 mg of rifaximin daily and cautiously to the subject if the subject'"'"'s Child-Pugh score is Child-Pugh Class C or if the subject'"'"'s MELD score is 25 or greater.

2. The method of claim 1, wherein the hepatic insufficiency is hepatic encephalopathy.

3. The method of claim 1, wherein the subject is treated for 12 to 72 hours.

4. The method of claim 1, wherein the subject is administered 1100 mg of rifaximin daily or 550 mg of rifaximin BID.

5. The method of claim 1, further comprising testing the subject for hepatic insufficiency.

6. The method of claim 1, wherein the TD is caused by bacterial, virus, or protozoan infection.

7. The method of claim 1, wherein the TD is caused by E. coli.

8. The method of claim 7, wherein the E. coli is enterotoxigenic E. coli.

9. The method of claim 1, wherein the subject is a human.

10. The method of claim 1, wherein systemic exposure of rifaximin is markedly elevated in patients with hepatic impairment compared to healthy subjects.

11. The method of claim 1, wherein the rifaximin comprises tablets for oral administration comprising one or more of colloidal silicon dioxide, disodium edetate, glycerol palmitostearate, hypromellose, microcrystalline cellulose, propylene glycol, red iron oxide, sodium starch glycolate, talc, or titanium dioxide.

12. The method of claim 1, wherein the duration of diarrhea was significantly shorter in a subject treated with rifaximin compared to an untreated subject.

13. The method of claim 1, wherein the clearance rate of rifaximin is decreased in a population of subjects with hepatic insufficiency as compared to population of subjects without hepatic insufficiency.

14. The method of claim 1, wherein the elimination rate of rifaximin is decreased in subjects with hepatic insufficiency as compared to subjects without hepatic insufficiency.

15. The method of claim 1, wherein the systemic exposure to rifaximin is increased in a population of subjects with hepatic insufficiency as compared to population of subjects without hepatic insufficiency.

16. The method of claim 1, wherein the serum level of rifaximin is increased in a population of subjects with hepatic insufficiency as compared to population of subjects without hepatic insufficiency.

17. A method of treating a patient suffering from hepatic encephalopathy (HE) comprising:

identifying a subject having Traveler'"'"'s Diarrhea (TD) that also has HE;

determining the severity of the subject'"'"'s HE; and

administering between 1000 and 1200 mg of rifaximin daily and cautiously to the subject if the HE is severe.

18. The method of claim 17, wherein the subject is administered 1100 mg of rifaximin.

19. The method of claim 18, wherein the subject is administered 550 mg of rifaximin BID.

20. The method of claim 17, wherein the subject is a human.

21. The method of claim 17, wherein the rifaximin comprises tablets for oral administration comprising one or more of colloidal silicon dioxide, disodium edetate, glycerol palmitostearate, hypromellose, microcrystalline cellulose, propylene glycol, red iron oxide, sodium starch glycolate, talc, or titanium dioxide.

22. The method of claim 17, further comprising determining if the subject'"'"'s Child-Pugh score is Child-Pugh Class C.

23. The method of claim 17, further comprising determining if the subject'"'"'s model end stage liver disease (MELD) score is 25 or greater.