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A method is disclosed for improving the pharmacokinetics of a drug which is metabolized by cytochrome P450 monooxygenase.

Inventors: Daniel W. Norbeck, Dale J. Kempf, John M. Leonard, Richard J. Bertz
Original Assignee: Abbott Laboratories
Primary Examiner: James O. Wilson
Secondary Examiner: Traviss C. McIntosh, III
Attorney: Steven R. Crowley
Current U.S. Classification: 514/300; 435/184; 514/365; 548/204; 548/205
International Classification: A01N/4342; A01N/4378; A61K/3144; A61K/31425

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Citations

Cited PatentFiling dateIssue dateOriginal AssigneeTitle
US5142056May 9, 1990Aug 25, 1992Abbott LaboratoriesRetroviral protease inhibiting compounds
US5196438Nov 19, 1990Mar 23, 1993Hoffmann-La Roche Inc.Amino acid derivatives
US5354866Sep 14, 1993Oct 11, 1994Abbott LaboratoriesRetroviral protease inhibiting compounds
US5413999May 7, 1993May 9, 1995Merck & Co., Inc.HIV protease inhibitors useful for the treatment of AIDS
US5484801May 12, 1995Jan 16, 1996Abbott LaboratoriesPharmaceutical composition for inhibiting HIV protease
US5484926Feb 2, 1994Jan 16, 1996Agouron Pharmaceuticals, Inc.HIV protease inhibitors
US5567823Jun 6, 1995Oct 22, 1996Abbott LaboratoriesProcess for the preparation of an HIV protease inhibiting compound
US5674882Mar 29, 1995Oct 7, 1997Abbott LaboratoriesRetroviral protease inhibiting compounds
US5886036Mar 20, 1997Mar 23, 1999Abbott LaboratoriesRetroviral protease inhibiting compounds
US6037157Jun 26, 1996Mar 14, 2000Abbott LaboratoriesMethod for improving pharmacokinetics
US6054490Apr 10, 1998Apr 25, 2000Zylepsis LimitedUse of sesquiterpenes for inhibiting oxidative enzymes

Referenced by

Citing PatentFiling dateIssue dateOriginal AssigneeTitle
US7388008Aug 2, 2004Jun 17, 2008Ambrilia Biopharma Inc.Lysine based compounds
US7763731Dec 20, 2006Jul 27, 2010Abbott LaboratoriesAnti-viral compounds
US7786153Mar 2, 2006Aug 31, 2010Abbott Laboratories Inc.Compounds that are useful for improving pharmacokinetics
US7910595Dec 20, 2006Mar 22, 2011Abbott LaboratoriesAnti-viral compounds
US7915411Dec 20, 2006Mar 29, 2011Abbott LaboratoriesAnti-viral compounds
US8008297Apr 4, 2008Aug 30, 2011Ambrilia Biopharma Inc.Lysine based compounds
US8025899Aug 25, 2004Sep 27, 2011Abbott LaboratoriesSolid pharmaceutical dosage form
US8227450Nov 30, 2006Jul 24, 2012Ambrilia Biopharma Inc.Lysine-based prodrugs of aspartyl protease inhibitors and processes for their preparation
US8232246Jun 30, 2009Jul 31, 2012Abbott LaboratoriesAnti-viral compounds

Claims

1. A method for inhibiting cytochrome P450 monooxygenase 3A4 comprising administering to a human in need thereof an amount of ritonavir or a pharmaceutically acceptable salt thereof effective to inhibit cytochrome P450 monooxygenase 3A4.

2. A method for inhibiting cytochrome P450 monooxygenase 3A4 comprising contacting the cytochrome P450 monooxygenase 3A4 with an amount of ritonavir or a pharmaceutically acceptable salt thereof effective to inhibit cytochrome P450 monooxygenase 3A4.

3. A method for improving the pharmacokinetics of a drug which is metabolized by cytochrome P450 monooxygenase comprising coadministering to a human being treated with said drug or a pharmaceutically acceptable salt thereof an amount effective to inhibit cytochrome P450 monooxygenase of ritonavir or a pharmaceutically acceptable salt thereof.

4. The method of claim 3 wherein the drug which is metabolized by cytochrome P450 monooxygenase is an HIV protease inhibitor.

5. The method of claim 3 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of cyclosporine, FK-506, rapamycin, taxol, taxotere, clarithromycin, A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

6. The method of claim 3 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437 CGP 57813 and U-103017.

7. The method of claim 3 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478 and AG1343.

8. The method of claim 3 wherein the drug which is metabolized by cytochrome P450 monooxygenase is saquinavir.

9. The method of claim 3 wherein the drug which is metabolized by cytochrome P450 monooxygenase is MK-639.

10. The method of claim 3, wherein the drug which is metabolized by cytochrome P450 monooxygenase is VX-478.

11. The method of claim 3, wherein the drug which is metabolized by cytochrome P450 monooxygenase is AG1343.

12. The method of claim 3, wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

13. The method of claim 4, wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

14. The method of claim 5, wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

15. The method of claim 6 the cytochrome P450 monooxygenase is cytochrome P450 3A4.

16. The method of claim 7 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

17. The method of claim 8 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

18. The method of claim 9 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

19. The method of claim 10 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

20. The method of claim 11 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

21. A method for improving the pharmacokinetics of a drug which is metabolized by cytochrome P450 monooxygenase comprising administering to a human in need of such treatment an amount effective to inhibit cytochrome P450 monooxygenase of ritonavir or a pharmaceutically acceptable salt thereof.

22. The method of claim 21 wherein the drug which is metabolized by cytochrome P450 monooxygenase is an HIV protease inhibitor.

23. The method of claim 21 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of cyclosporine, FK-506, rapamycin, taxol, taxotere, clarithromycin, A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

24. The method of claim 21 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

25. The method of claim 21 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of A-77003, AI-80987, MK-639, saquinavir, VX-478 and AG1343.

26. The method of claim 21 wherein the drug which is metabolized by cytochrome P450 monooxygenase is saquinavir.

27. The method of claim 21 wherein the drug which is metabolized by cytochrome P450 monooxygenase is MK-639.

28. The method of claim 21 wherein the drug which is metabolized by cytochrome P450 monooxygenase is VX-478.

29. The method of claim 21 wherein the drug which is metabolized by cytochrome P450 monooxygenase is AG1343.

30. The method of claim 21 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

31. The method of claim 22 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

32. The method of claim 23 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

33. The method of claim 24 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

34. The method of claim 25 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

35. The method of claim 26 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

36. The method of claim 27 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

37. The method of claim 28 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

38. The method of claim 29 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

39. A method for improving the pharmacokinetics of a drug which is metabolized by cytochrome P450 monooxygenase 3A4 comprising administering to a human in need of such treatment a therapeutically effective amount of a combination of said drug or a pharmaceutically acceptable salt thereof and ritonavir or a pharmaceutically acceptable salt thereof.

40. The method of claim 39 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is an HIV protease inhibitor.

41. The method of claim 39 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is selected from the group consisting of cyclosporine, FK-506, rapamycin, taxol, taxotere, clarithromycin, A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

42. The method of claim 39 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

43. The method of claim 39 the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478 and AG1343.

44. The method of claim 39 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is saquinavir.

45. The method of claim 39 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is MK-639.

46. The method of claim 39 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is VX-478.

47. The method of claim 39 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is AG1343.

48. A method for increasing the blood level of a drug which is metabolized by cytochrome P450 monooxygenase comprising coadministering to a human being treated with said drug or a pharmaceutically acceptable salt thereof an amount effective to inhibit cytochrome P450 monooxygenase of ritonavir or a pharmaceutically acceptable salt thereof.

49. The method of claim 48 wherein the drug which is metabolized by cytochrome P450 monooxygenase is an HIV protease inhibitor.

50. The method of claim 48 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of cyclosporine, FK-506, rapamycin, taxol, taxotere, clarithromycin, A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

51. The method of claim 48 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

52. The method of claim 48 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478 and AG1343.

53. The method of claim 48 wherein the drug which is metabolized by cytochrome P450 monooxygenase is saquinavir.

54. The method of claim 48 wherein the drug which is metabolized by cytochrome P450 monooxygenase is MK-639.

55. The method of claim 48 wherein the drug which is metabolized by cytochrome P450 monooxygenase is VX-478.

56. The method of claim 48 wherein the drug which is metabolized by cytochrome P450 monooxygenase is AG1343.

57. The method of claim 48 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

58. The method of claim 49 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

59. The method of claim 50 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

60. The method of claim 51 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

61. The method of claim 52 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

62. The method of claim 53 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

63. The method of claim 54 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

64. The method of claim 55 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

65. The method of claim 56 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

66. A method for increasing the blood level of a drug which is metabolized by cytochrome P450 monooxygenase comprising administering to a human in need of such treatment an amount effective to inhibit cytochrome P450 monooxygenase of ritonavir or a pharmaceutically acceptable salt thereof.

67. The method of claim 66 wherein the drug which is metabolized by cytochrome P450 monooxygenase is an HIV protease inhibitor.

68. The method of claim 66 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of cyclosporine, FK-506, rapamycin, taxol, taxotere, clarithromycin, A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

69. The method of claim 66 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

70. The method of claim 66 wherein the drug which is metabolized by cytochrome P450 monooxygenase is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478 and AG1343.

71. The method of claim 66 wherein the drug which is metabolized by cytochrome P450 monooxygenase is saquinavir.

72. The method of claim 66 wherein the drug which is metabolized by cytochrome P450 monooxygenase is MK-639.

73. The method of claim 66 wherein the drug which is metabolized by cytochrome P450 monooxygenase is VX-478.

74. The method of claim 66 wherein the drug which is metabolized by cytochrome P450 monooxygenase is AG1343.

75. The method of claim 66 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

76. The method of claim 67 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

77. The method of claim 68 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

78. The method of claim 69 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

79. The method of claim 70 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

80. The method of claim 71 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

81. The method of claim 72 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

82. The method of claim 73 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

83. The method of claim 74 wherein the cytochrome P450 monooxygenase is cytochrome P450 3A4.

84. A method for increasing the blood level of a drug which is metabolized by cytochrome P450 monooxygenase 3A4 comprising administering to a human in need of such treatment a therapeutically effective amount of a combination of said drug or a pharmaceutically acceptable salt thereof and ritonavir or a pharmaceutically acceptable salt thereof.

85. The method of claim 84 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is an HIV protease inhibitor.

86. The method of claim 84 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is selected from the group consisting of cyclosporine, FK-506, rapamycin, taxol, taxotere, clarithromycin, A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

87. The method of claim 84 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478, AG1343, DMP-323, XM-450, BILA 2011 BS, BILA 1096 BS, BILA 2185 BS, BMS 186,318, LB71262, SC-52151, SC-629, KNI-272, CGP 53437, CGP 57813 and U-103017.

88. The method of claim 84 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is selected from the group consisting of A-77003, A-80987, MK-639, saquinavir, VX-478 and AG1343.

89. The method of claim 84 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is saquinavir.

90. The method of claim 84 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is MK-639.

91. The method of claim 84 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is VX-478.

92. The method of claim 84 wherein the drug which is metabolized by cytochrome P450 monooxygenase 3A4 is AG1343.