Details for Patent: 6,703,403

Title:	Method for improving pharmacokinetics
Abstract:	A method is disclosed for improving the pharmacokinetics of a drug which is metabolized by cytochrome P450 monooxygenase.
Inventor(s):	Norbeck; Daniel W. (Crystal Lake, IL), Kempf; Dale J. (Libertyville, IL), Leonard; John M. (Lake Bluff, IL), Bertz; Richard J. (Kenosha, WI)
Assignee:	Abbott Laboratories (Abbott Park, IL)
Filing Date:	Sep 20, 2001
Application Number:	09/957,171
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.