Methods of treating travelers diarrhea and hepatic encephalopathy

• US 7,928,115 B2
• Filed: 12/01/2010
• Issued: 04/19/2011
• Est. Priority Date: 10/02/2008
• Status: Active Grant

• Current Assignee: Salix Pharmaceuticals Incorporated (Bausch Health Cos., Inc.)
• Original Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Inventors: Bortey, Enoch, Forbes, William
• Primary Examiner(s): Spivack; Phyllis G.
• Application Number:
  US12/957,831
• Publication Number:
  US 20110065740A1
• Time in Patent Office: 139 Days
• Field of Search: None
• US Class Current: 514/285
• 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 in subjects having hepatic encephalopathy using rifaximin is disclosed.

Claims

1. A method of treating a subject having Travelers'"'"' Diarrhea (TD) comprising:

identifying a subject having 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;

administering rifaximin cautiously to the subject if his or her Child-Pugh score is Child-Pugh Class C or if his or her 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 rifaximin is administered at 200 mg TID.

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 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.

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

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

13. 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.

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

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