Details for Patent: 6,669,948

Title:	Antibiotic product, use and formulation thereof
Abstract:	An antibiotic product, in particular a betalactam such as cephalosporin (in particular cefuroxime and/or cefpodoxime) or a penicillin (in particular axmoxicillin or dicloxacillin) is comprised of at least three dosages forms, each of which has a different release profile, with the C.sub.max for the antibiotic product being reached in less than about twelve hours. In one embodiment, there is an immediate release dosage form, as well as two or more delayed release dosage forms, with each of the dosage forms having a different release profile, wherein each reaches a C.sub.max at different times.
Inventor(s):	Rudnic; Edward M. (N. Potomac, MD), Isbister; James D. (Potomac, MD), Treacy, Jr.; Donald J. (Arnold, MD), Wassink; Sandra E. (Frederick, MD)
Assignee:	Advancis Pharmaceutical Corp. (Germantown, MD)
Filing Date:	Dec 20, 2001
Application Number:	10/027,609
Claims:	1. A once-a-day antibiotic product comprising: first, second, and third dosage forms; each of said dosage forms comprising a betalactam antibiotic and a pharmaceutically acceptable carrier; said first dosage form being an immediate release dosage form; said second and third dosage forms being delayed release dosage forms; wherein each of said first, second, and third dosage forms initiates release of the betalactam antibiotic at different times; wherein Cmax of the total betalactam antibiotic released from said product is achieved in less than about 12 hours from administration; and wherein said once-a-day product contains the total dosage of the betalactam antibiotic for a twenty-four hour period. 2. The antibiotic product of claim 1, wherein said betalactam antibiotic is a cephalosporin. 3. The antibiotic product of claim 2, wherein said cephalosporin is selected from the group consisting of cefuroxime and cefpodoxime. 4. The product of claim 3, wherein the Cmax for the product is reached no earlier than four hours after administration. 5. The product of claim 3, wherein the cephalosporin released from the first dosage form reaches a Cmax within from about 0.5 hours to about 2 hours after administration of the product. 6. The product of claim 3, wherein the cephalosporin released from the second dosage form reaches a Cmax in no more than about 4 hours after administration of the product. 7. The product of claim 3, wherein the cephalosporin released from the third dosage form reaches a Cmax within 8 hours after administration of the product. 8. The product of claim 3, wherein the immediate release dosage form contains at least 20% and no more than 50% of the total dosage of cephalosporin. 9. The product of claim 3, wherein the product is an oral dosage form. 10. The product of claim 3, wherein the cephalosporin released from the second dosage form reaches a Cmax after Cmax is reached for the cephalosporin released from the first dosage form. 11. The product of claim 3, wherein the cephalosporin released from the third dosage form reaches a Cmax after Cmax is reached for the cephalosporin released from the second dosage form. 12. The product of claim 3 further comprising a fourth dosage form, said fourth dosage form being a delayed release dosage form comprising cephalosporin and a pharmaceutically acceptable carrier; and wherein cephalosporin released from said fourth dosage form reaches a Cmax after Cmax is achieved for cephalosporin released from each of said first, second, and third dosage forms. 13. The product of claim 12, wherein the Cmax for the product is reached no earlier than four hours after administration. 14. The product of claim 12, wherein the cephalosporin released from the first dosage form reaches a Cmax within from about 0.5 hours to about 2 hours after administration of the product. 15. The product of claim 12, wherein the cephalosporin released from the second dosage form reaches a Cmax in no more than about 4 hours after administration of the product. 16. The product of claim 12, wherein the cephalosporin released from the third dosage form reaches a Cmax within 8 hours after administration of the product. 17. The product of claim 12, wherein said second dosage form initiates release of cephalosporin before said third dosage form, wherein said third dosage form initiates release of cephalosporin before said fourth dosage form, wherein said second dosage form provides 20% to 35% by weight of the total cephalosporin released by said second, third, and fourth dosage forms, wherein said third dosage form provides from 20% to 40% by weight of the total cephalosporin released by said second, third, and fourth dosage forms, and wherein said fourth dosage form provides the remainder of the total cephalosporin released by said second, third, and fourth dosage forms. 18. The product of claim 12, wherein the product is an oral dosage form. 19. The product of claim 12, wherein the cephalosporin released from the second dosage form reaches a Cmax after Cmax is reached for the cephalosporin released from the first dosage form. 20. The product of claim 12, wherein the cephalosporin released from the third dosage form reaches a Cmax after Cmax is reached for the cephalosporin released from the second dosage form. 21. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 1, once-a-day. 22. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 2, once-a-day. 23. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 3, once-a-day. 24. A process for treating a bacterial infection in a host comprising: administering to a host the cephalosporin product of claim 4, once-a-day. 25. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 5, once-a-day. 26. A process for treating a, bacterial infection in a host comprising: administering to a host the product of claim 6, once-a-day. 27. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 7, once-a-day. 28. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 8, once-a-day. 29. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 9, once-a-day. 30. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 10, once-a-day. 31. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 11, once-a-day. 32. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 12, once-a-day. 33. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 13, once-a-day. 34. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 14, once-a-day. 35. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 15, once-a-day. 36. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 16, once-a-day. 37. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 17, once-a-day. 38. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 18, once-a-day. 39. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 19, once-a-day. 40. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 20, once-a-day. 41. The antibiotic product of claim 3, wherein said cephalosporin is cefuroxime. 42. The antibiotic product of claim 3, wherein said cephalosporin is cefpodoxime. 43. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 41, once-a-day. 44. A process for treating a bacterial infection in a host comprising: administering to a host the product of claim 42, once-a-day. 45. The antibiotic product of claim 11, wherein said betalactam antibiotic is a penicillin. 46. The antibiotic product of claim 45, wherein said penicillin is selected from the group consisting of dicloxacillin and amoxicillin. 47. The product of claim 46, wherein the Cmax for the product is reached no earlier than four hours after administration. 48. The product of claim 46, wherein penicillin released from the first dosage form reaches a Cmax within from about 0.5 hours to about 2 hours after administration of the product. 49. The product of claim 46, wherein the penicillin released from the second dosage form reaches a Cmax in no more than about 4 hours after administration of the product. 50. The product of claim 46, wherein the penicillin released from the third dosage form reaches a Cmax within 8 hours after administration of the product. 51. The product of claim 46, wherein the immediate release dosage form contains at least 20% and no more than 50% of the total dosage of the penicillin. 52. The product of claim 46, wherein the product is an oral dosage form. 53. The product of claim 46, wherein the penicillin released from the second dosage form reaches a Cmax after Cmax is reached for the penicillin released from the first dosage form. 54. The product of claim 46, wherein the penicillin released from the third dosage form reaches a Cmax after Cmax is reached for the penicillin released from the second dosage form. 55. The product of claim 46, further comprising a fourth dosage form, said fourth dosage form being a delayed release dosage form comprising said penicillin and a pharmaceutically acceptable carrier; and wherein said penicillin released from said fourth dosage form reaches a Cmax after Cmax is achieved for penicillin released from each of said first, second, and third dosage forms. 56. The product of claim 55, wherein the Cmax for the product is reached no earlier than four hours after administration. 57. The product of claim 55, wherein the penicillin released from the first dosage form reaches a Cmax within from about 0.5 hours to about 2 hours after administration of the product. 58. The product of claim 55, wherein the penicillin released from the second dosage form reaches a Cmax in no more than about 4 hours after administration of the product. 59. The product of claim 55, wherein the penicillin released from the third dosage form reaches a Cmax within 8 hours after administration of the product. 60. The product of claim 55, wherein said second dosage form initiates release of said penicillin before said third dosage form, wherein said third dosage form initiates release of said penicillin before said fourth dosage form, wherein said second dosage form provides 20% to 35% by weight of the total penicillin released by said second, third, and fourth dosage forms, wherein said third dosage form provides from 20% to 40% by weight of the total penicillin released by said second, third, and fourth dosage forms, and wherein said fourth dosage form provides the remainder of the total penicillin released by said second, third, and fourth dosage forms. 61. The product of claim 55, wherein the product is an oral dosage form. 62. The product of claim 55, wherein the penicillin released from the second dosage form reaches a Cmax after Cmax is reached for the penicillin released from the first dosage form. 63. The product of claim 55, wherein the penicillin released from the third dosage form reaches a Cmax after Cmax is reached for the penicillin released from the second dosage form. 64. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 45, once-a-day. 65. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 46, once-a-day. 66. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 47, once-a-day. 67. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 48, once-a-day. 68. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 49, once-a-day. 69. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 50, once-a-day. 70. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 57, once-a-day. 71. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 52, once-a-day. 72. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 53, once-a-day. 73. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 54, once-a-day. 74. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 55, once-a-day. 75. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 56, once-a-day. 76. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 57, once-a-day. 77. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 58, once-a-day. 78. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 59, once-a-day. 79. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 60, once-a-day. 80. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 61, once-a-day. 81. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 62, once-a-day. 82. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 63, once-a-day. 83. The antibiotic product of claim 45, said penicillin is dicloxacillin. 84. A process for treating a bacterial infection in a host comprising: administering to a host the penicillin product of claim 83, once-a-day. 85. A once-a-day antibiotic product comprising: first, second, and third dosage forms; each of said dosage forms comprising amoxicillin and a pharmaceutically acceptable carrier; said first dosage form being an immediate release dosage form; said second and third dosage forms being delayed release dosage forms; wherein each of said first, second, and third dosage forms initiates release of amoxicillin at different times; wherein Cmax of the total amoxicillin released from said product is achieved in less than about 12 hours from administration; and wherein said once-a-day product contains the total dosage of amoxicillin for a twenty-four hour period. 86. The product of claim 85, wherein the Cmax for the product is reached no earlier than four hours after administration. 87. The product of claim 85, wherein the amoxicillin released from the first dosage form reaches a Cmax within from about 0.5 hours to about 2 hours after administration of the product. 88. The product of claim 85, wherein the amoxicillin released from the second dosage form reaches a Cmax in no more than about 4 hours after administration of the product. 89. The product of claim 85, wherein the amoxicillin released from the third dosage form reaches a Cmax within 8 hours after administration of the product. 90. The product of claim 85, wherein the immediate release dosage form contains at least 20% and no more than 50% of the total dosage of amoxicillin. 91. The product of claim 85, wherein the product is an oral dosage form. 92. The product of claim 85, wherein the amoxicillin released from the second dosage form reaches a Cmax after Cmax is reached for the amoxicillin released from the first dosage form. 93. The product of claim 85, wherein the amoxicillin released from the third dosage form reaches a Cmax after Cmax is reached for the amoxicillin released from the second dosage form. 94. The product of claim 85, further comprising a fourth dosage form, said fourth dosage form being a delayed release dosage form comprising amoxicillin and a pharmaceutically acceptable carrier; and wherein amoxicillin released from said fourth dosage form reaches a Cmax after Cmax is achieved for amoxicillin released from each of said first, second, and third dosage forms. 95. The product of claim 94, wherein the Cmax for the product is reached no earlier than four hours after administration. 96. The product of claim 94, wherein the amoxicillin released from the first dosage form reaches a Cmax within from about 0.5 hours to about 2 hours after administration of the product. 97. The product of claim 94, wherein the amoxicillin released from the second dosage form reaches a Cmax in no more than about 4 hours after administration of the product. 98. The product of claim 94, wherein the amoxicillin released from the third dosage form reaches a Cmax within 8 hours after administration of the product. 99. The product of claim 94, wherein said second dosage form initiates release of amoxicillin before said third dosage form, wherein said third dosage form initiates release of amoxicillin before said fourth dosage form, wherein said second dosage form provides 20% to 35% by weight of the total amoxicillin released by said second, third, and fourth dosage forms, wherein said third dosage form provides from 20% to 40% by weight of the total amoxicillin released by said second, third, and fourth dosage forms, and wherein said fourth dosage form provides the remainder of the total amoxicillin released by said second, third, and fourth dosage forms. 100. The product of claim 94, wherein the product is an oral dosage form. 101. The product of claim 94, wherein the amoxicillin released from the second dosage form reaches a Cmax after Cmax is reached for the amoxicillin released from the first dosage form. 102. The product of claim 94, wherein the amoxicillin released from the third dosage form reaches a Cmax after Cmax is reached for the amoxicillin released from the second dosage form. 103. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 85, once-a-day. 104. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 86, once-a-day. 105. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 87, once-a-day. 106. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 88, once-a-day. 107. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 89, once-a-day. 108. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 90, once-a-day. 109. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 91, once-a-day. 110. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 92, once-a-day. 111. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 93, once-a-day. 112. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 94, once-a-day. 113. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 95, once-a-day. 114. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 96, once-a-day. 115. A process for treating a bacterial 97, infection in a host comprising: administering to a host the amoxicillin product of claim 97, once-a-day. 116. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 98, once-a-day. 117. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 99, once-a-day. 118. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 100, once-a-day. 119. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 101, once-a-day. 120. A process for treating a bacterial infection in a host comprising: administering to a host the amoxicillin product of claim 102, once-a-day.