Methods for administration of antibiotics

• US 6,852,689 B2
• Filed: 02/20/2002
• Issued: 02/08/2005
• Est. Priority Date: 09/25/1998
• Status: Expired due to Term

• Current Assignee: Cubist Pharmaceuticals, LLC (Merck & Co., Inc.)
• Original Assignee: Cubist Pharmaceuticals, Inc. (Merck & Co., Inc.)
• Inventors: Oleson, Frederick B. Jr., Tally, Francis P.
• Primary Examiner(s): Clardy, S. Mark
• Assistant Examiner(s): CHOI, FRANK I
• Application Number:
  US10/082,544
• Publication Number:
  US 20020142948A1
• Time in Patent Office: 1,084 Days
• Field of Search: 424/114, 424/116, 514/9, 514/11, 514/183, 530/317
• US Class Current: 514/2.9
• 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 daptomycin, comprising the step of administering to a human patient in need thereof a therapeutically effective amount of daptomycin in a dose of at least 3 mg/kg of daptomycin at a dosage interval that minimizes skeletal muscle toxicity, wherein the daptomycin dose is repeatedly administered at a dosage interval of once every 48 hours to once weekly.

2. The method according to claim 1, wherein the dose is 3 to 12 mg/kg.

3. The method according to claim 2, wherein the dose is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 mg/kg.

4. The method according to claim 1, wherein the dose is 10 to 25 mg/kg.

5. The method according to claim 4, wherein the dose is 10, 11, 12, 13, 14, 15, 16, 20 or 25 mg/kg.

6. The method according to claim 1, wherein an antibiotic other than daptomycin is co-administered with the lipopeptide antibiotic.

7. The method according to claim 6, 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.

8. The method according to claim 6, wherein said antibiotic is selected from the group consisting of imipenen, amikacin, netilmicin, fosfomycin, gentamicin and teicoplanin.

9. The method according to claim 6, wherein said administering is via oral, subcutaneous or intravenous administration.

10. The method according to claim 1, wherein said administering is via oral, subcutaneous or intravenous administration.

11. The method according to claim 1 wherein the daptomycin dose is repeatedly administered at a dosage interval of once every 48 hours to once every 96 hours.

12. The method according to claim 11 wherein the dosage interval is once every 72 hours.

13. The method according to claim 11 wherein the dosage interval is once every 96 hours.

14. The method according to claim 11, wherein the dose is 3 to 12 mg/kg.

15. The method according to claim 14, wherein the dose is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 mg/kg.

16. The method according to claim 14, wherein the dose is 4, 6, 8 or 10 mg/kg.

17. The method according to claim 14 wherein the dose is 4 mg/kg.

18. The method according to claim 14 wherein the dose is 6 mg/kg.

19. The method according to claim 11 wherein the dose is 25 to 75 mg/kg.

20. The method according to claim 19 wherein the dose is 25, 50 or 75 mg/kg.

21. The method according to claim 11, wherein the dose is 10 to 25 mg/kg.

22. The method according to claim 21, wherein the dose is 10, 11, 12, 13, 14, 15, 16, 20 or 25 mg/kg.

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

24. The method according to claim 11, wherein the daptomycin is administered for 2 days to 6 months.

25. The method according to claim 11, wherein the daptomycin is administered for 7 to 28 days.

26. The method according to claim 11, wherein the daptomycin is administered for 7 to 14 days.

27. A method for treating or eradicating a bacterial infection in a human patient in need thereof, comprising the step of administering a therapeutically effective amount of daptomycin in a dose of 3 to 75 mg/kg to the patient at a dosage interval that minimizes skeletal muscle toxicity, wherein the daptomycin dose is repeatedly administered at a dosage interval of once every 48 hours to once weekly, until said bacterial infection is treated or eradicated.

28. The method according to claim 27 wherein the dosage interval is once every 48 hours to once every 96 hours.

29. The method according to claim 28 wherein the dosage interval is once every 48 hours.

30. The method according to claim 28 wherein the dosage interval is once every 72 hours.

31. The method according to claim 28 wherein the dosage interval is once every 96 hours.

32. The method according to claim 27, wherein the dose is 3 to 12 mg/kg.

33. The method according to claim 27, wherein the dose is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 mg/kg.

34. The method according to claim 27, wherein the dose is 25 to 75 mg/kg.

35. The method according to claim 34 wherein the dose is 25, 50 or 75 mg/kg.

36. The method according to claim 27, wherein the dose is 10 to 25 mg/kg.

37. The method according to claim 36, wherein the dose is 10, 11, 12, 13, 14, 15, 16, 20 or 25 mg/kg.

38. The method according to claim 37, wherein the dose is 4 mg/kg.

39. The method according to claim 38, wherein the daptomycin is administered for 7 to 28 days.

40. The method according to claim 38, wherein the daptomycin is administered for 7 to 14 days.

41. The method according to claim 37, wherein the dose is 6 mg/kg.

42. The method according to claim 41, wherein the daptomycin is administered for 7 to 14 days.

43. The method according to claim 41, wherein the daptomycin is administered for 7 to 28 days.

44. The method according to claim 27, wherein the daptomycin is administered for 2 days to 6 months.

45. The method according to claim 27, wherein the daptomycin is administered for 7 to 28 days.

46. The method according to claim 27, wherein the daptomycin is administered for 7 to 14 days.

47. A method for administering daptomycin, comprising the step of administering to a human patient in need thereof a tharapeutically effective amount of daptomycin in a dose of at least 3 mg/kg of daptomycin at a dosage interval that minimizes skeletal muscle toxicity, wherein the dose is repeatedly administered at a dosage interval of once every 48 hours.

48. The method according to claim 47, wherein the dose is 3 to 12 mg/kg.

49. The method according to claim 48, wherein the dose is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 mg/kg.

50. The method according to claim 48, wherein the dose is 4, 6, 8 or 10 mg/kg.

51. The method according to claim 48 wherein the dose is 4 mg/kg.

52. The method according to claim 48 wherein the dose is 6 mg/kg.

53. The method according to claim 48 wherein the dose is 8 mg/kg.

54. The method according to claim 47, wherein said administering is via oral, subcutaneous or intravenous administration.

55. The method according to claim 47, wherein the daptomycin is administered for 2 days to 6 months.

56. The method according to claim 47, wherein the daptomycin is administered for 7 to 28 days.

57. The method according to claim 47, wherein the daptomycin is administered for 7 to 14 days.