Methods for administration of antibiotics

• US 20020142948A1
• Filed: 02/20/2002
• Published: 10/03/2002
• Est. Priority Date: 09/25/1998
• Status: Active Grant

• Current Assignee: Cubist Pharmaceuticals, LLC (Merck & Co., Inc.)
• Original Assignee: Cubist Pharmaceuticals, Inc. (Merck & Co., Inc.)
• Inventors: Tally, Francis P., Oleson, Frederick B. Jr.
• Granted Patent: US 6,852,689 B2
• Time in Patent Office: Days
• US Class Current: 514/9
• 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 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents

Abstract

The invention provides methods for administering a therapeutically effective amount of daptomycin while minimizing skeletal muscle toxicity. The methods provide daptomycin administration at a dosing interval of 24 hours or greater. This long dosing interval minimizes skeletal muscle toxicity and allows for higher peak concentrations of daptomycin, which is related to daptomycin'"'"'s efficacy The invention also provides methods of administering lipopeptide antibiotics other than daptomycin while minimizing skeletal muscle toxicity by administering a therapeutically effective amount of the lipopeptide antibiotic at a dosage interval that does not result in muscle toxicity. The invention also provides methods of administering quinupristin/dalfopristin while minimizing skeletal muscle toxicity by administering a therapeutically effective amount of quinupristin/dalfopristin at a dosage interval that dos not result in muscle toxicity.

Claims

1. A method for administering a lipopeptide antibiotic, comprising the step of administering to a patient in need thereof a therapeutically effective amount of the lipopeptide antibiotic at a dosage interval that does not result in muscle toxicity.

2. The method according to claim 1, wherein the lipopeptide antibiotic is administered once every 24 hours to once weekly.

3. The method according to claim 2, wherein the lipopeptide antibiotic is administered once every 24 hours, 48 hours, 72 hours or 96 hours

4. The method according to claim 1, wherein the lipopeptide antibiotic is selected from the group consisting of daptomycin, a daptomycin derivative, A54145 and a A54145 derivative.

5. The method according to claim 4, wherein the lipopeptide antibiotic is daptomycin.

11. The method according to either of claim 1 or claim 6, wherein an antibiotic other than a lipopeptide antibiotic is co-administered with the lipopeptide antibiotic.

12. The method according to claim 11 wherein said lipopeptide antibiotic is daptomycin.

13. The method according to claim 11, wherein said antibiotic is selected from the group consisting of penicillins and related drugs, carbapenems, cephalosporins and related drugs, aminoglycosides, bacitracin, gramicidin, mupirocin, chloramphenicol, thiamphenicol, ftsidate sodium, lincomycin, clindamycin, macrolides, novobiocin, polymyxins, rifamycins, spectinomycin, tetracyclines, vancomycin, teicoplanin, streptogramins, anti-folate agents, sulfonamides, trimethoprim and its combinations, pyrimethamine, synthetic antibacterials, nitrofurans, methenamine mandelate, methenamine hippurate, nitroimidazoles, quinolones, fluoroquinolones, isoniazid, ethambutol, pyrazinamide, para-aminosalicylic acid (PAS), cycloserine, capreomycin, ethionamide, prothionamide, thiacetazone and viomycin.

14. The method according to claim 11, wherein said antibiotic is selected from the group consisting of imipenen, amikacin, netilmicin, fosfomycin, gentamicin and teicoplanin.

15. The method according to claim 11, wherein said administering is via oral, subcutaneous or intravenous administration.

17. The method according to claim 16, wherein the dose is 3 to 12 mg/kg.

18. The method according to claim 17, wherein the dose is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 mg/kg.

19. The method according to claim 16, wherein the dose is 10 to 25 mg/kg.

20. The method according to claim 19, wherein the dose is 10, 11, 12, 13, 14, 15, 16, 20 or 25 mg/kg.

21. The method according to claim 17, wherein the dose is 25 to 75 mg/kg.

22. The method according to claim 21, wherein the dose is 25, 50 or 75 mg/kg.

23. The method according to claim 16, wherein said method reduces muscle toxicity compared to administration of daptomycin at a more frequent interval than 24 hours.

24. The method according to claim 18, wherein the dose is 4 mg/kg administered once every 24 hours.

25. The method according to claim 18, wherein the dose is 6 mg/kg administered once every 24 hours.

26. The method according to any one of claims 1, 6 or 16, wherein said administering is via oral, subcutaneous or intravenous administration.

28. The method according to claim 27, wherein quinupristin/dalfopristin is administered once every 24 hours to once weekly.

29. The method according to claim 28, wherein quinupristin/dalfopristin is administered once every 24 hours, 48 hours, 72 hours or 96 hours.

30. The method according to claim 27, wherein said quinupristin/dalfopristin is administered at a dose of 7.5 to 30 mg/kg.

31. The method according to claim 27, wherein said quinupristin/dalfopristin is administered at a dose of 7.5, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 or 30 mg/kg.

6. A method for administering daptomycin, comprising the step of administering to a patient in need thereof a therapeutically effective amount of daptomycin in a dose of 3 to 75 mg/kg of daptomycin, wherein the daptomycin is administered once every 24 hours to once weekly.

7. The method according to claim 6, wherein the dose is 3 to 12 mg/kg.

8. The method according to claim 7, wherein the dose is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 mg/kg.

9. The method according to claim 6, wherein the dose is 10 to 25 mg/kg.

10. The method according to claim 9, wherein the dose is 10, 11, 12, 13, 14, 15, 16, 20 or 25 mg/kg.

16. A method for administering daptomycin, comprising the step of administering to a patient or animal in need thereof a therapeutically effective amount of daptomycin at a dose of 3 to 75 mg/kg of daptomycin, wherein daptomycin is administered once every 24 hours.

27. A method for administering quinupristin/dalfopristin, comprising the step of administering to a patient in need thereof a therapeutically effective amount of quinupristin/dalfopristin at a dosage interval that does not result in muscle toxicity.

32. A pharmaceutical composition comprising a single dose of daptomycin and a pharmaceutically acceptable carrier, wherein said single dose is 7 to 15 mg/kg.

33. A pharmaceutical composition comprising a single dose of quinupristin/dalfopristin and a pharmaceutically acceptable carrier, wherein said single dose is 10 to 30 mg/kg.