Parenteral carbamazepine formulation
The present invention is directed to a carbamazepine-cyclodextrin inclusion complex useful for the parenteral administration of carbamazepine. The carbamazepine-cyclodextrin inclusion complex is prepared by the admixture of a modified cyclodextrin and carbamazepine in a physiologically acceptable fluid. Modified cyclodextrins include 2-hydroxypropyl-beta-cyclodextrin and sulfoalkyl cyclodextrins. More particularly, the sulfoalkyl cyclodextrins are those described and disclosed in U.S. Pat. Nos. 5,134,127 and 5,376,645. A physiologically acceptable fluid includes sterile isotonic water, Ringer's lactate, D5W (5% dextrose in water), physiological saline, and similar fluids suitable for parenteral administration.
1. A method of administering a carbamazepine sulfoalkyl-cylcodextrin composition to a human in need thereof comprising,
a) providing a carbamazepine sulfoalkyl-cyclodextrin composition, and
b) parenteraly infusing said composition to said human, wherein the composition is administered as a replacement for oral carbamazepine in a dose of about 30% to about 100% of the human's oral maintenance dose.
2. The method of claim 1 , wherein the sulfoalkyl-cyclodextrin is present at about 25% weight/volume.
3. The method of claim 1 , wherein the carbamazepine sulfoalkyl-cyclodextrin composition is administered in a daily dosage of about 65% to 75% of the human's daily oral dosage.
4. The method of claim 1 , wherein the sulfoalkyl-cyclodextrin is sulfobutylether-7β-cyclodextrin.
5. The method of claim 1 , wherein the composition comprises about 10 mg/mL carbamazepine.
6. The method of claim 1 , wherein the human has a seizure disorder.
7. The method of claim 6 , wherein the seizure disorder is selected from partial seizures with complex symptoms, generalized tonic-clonic seizures, mixed seizure patterns, epilepsy, status epilipticus and refractory seizure disorders.
8. The method of claim 7 , wherein the seizure disorder is epilepsy.
9. The method of claim 7 , wherein the seizure disorder is status epilipticus.
10. The method of claim 1 , wherein the composition is administered intravenously, intraarterially, intramuscularly, subcutaneously or intraperitonealy.
11. The method of claim 10 , wherein the composition is administered intravenously.
12. The method of claim 1 , wherein trough carbamazepine concentrations remain within the therapeutic range.
13. The method of claim 1 , wherein the area under plasma concentration-time curve (AUC) for carbamazepine is about 70% to about 130% of the AUC for the oral maintenance dose.
14. The method of claim 1 , wherein the area under plasma concentration-time curve (AUC) for carbamazepine is about 80% to about 125% of the AUC for the oral maintenance dose.
15. The method of claim 1 , wherein the minimum carbamazepine plasma concentration is about 70% to about 130% of the minimum plasma concentration for the oral maintenance dose.
16. The method of claim 1 , wherein the minimum carbamazepine plasma concentration is about 80% to about 125% of the minimum plasma concentration for the oral maintenance dose.
17. A method of administering a carbamazepine sulfoalkyl-cyclodextrin composition to a human having a seizure disorder comprising,
a) providing a carbamazepine sulfoalkyl-cyclodextrin composition, and
b) intravenously administering said composition to said human, wherein the composition is administered as a replacement for oral carbamazepine in a dose of about 30% to about 100% of the human's oral maintenance dose.
18. The method of claim 17 , wherein the sulfoalkyl-cyclodextrin is sulfobutylether-7β-cyclodextrin.
19. The method of claim 17 , wherein the composition comprises about 10 mg/mL carbamazepine and about 25% w/v sulfoalkyl-cyclodextrin.
20. The method of claim 17 , wherein the seizure disorder is epilepsy.
21. The method of claim 17 , wherein the seizure disorder is status epilipticus.
22. The method of claim 17 , wherein the seizure disorder is partial seizures with complex symptoms.
23. The method of claim 17 , wherein the seizure disorder is generalized tonic-clonic seizures.
24. The method of claim 17 , wherein the seizure disorder is mixed seizure patterns.
25. A method of administering a carbamazepine sulfobutylether-7-β-cyclodextrin composition to a human having epilepsy or status epilipticus comprising,
a) providing a carbamazepine sulfobutylether-7-β-cyclodextrin composition, wherein the composition comprises about 10 mg/mL carbamazepine and about 25% w/v sulfobutylether-7-β-cyclodextrin; and
b) intravenously administering the composition to said human, wherein the composition is administered as a replacement for oral carbamazepine in a daily dosage of about 65% to 75% of the human's daily oral dosage, and wherein administration occurs over a period from about 5 to about 60 minutes.
26. The method of claim 25 , wherein administration occurs over a period of about 30 minutes.
27. The method of claim 25 , wherein administration occurs over a period of about 15 minutes.
28. The method of claim 25 , wherein administration occurs over a period of about 5 minutes.
29. The method of claim 25 , further comprising a dosing interval of about every 4-12 hours.
30. The method of claim 25 , wherein the carbamazepine sulfobutylether-7-β-cyclodextrin composition is administered in a daily dosage of about 70% of the human's daily oral dosage.
31. The method of claim 25 , wherein trough carbamazepine concentrations remain within the therapeutic range.
32. The method of claim 25 , wherein the area under plasma concentration-time curve (AUC) for carbamazepine is about 70% to about 130% of the AUC for the oral maintenance dose.
33. The method of claim 25 , wherein the area under plasma concentration-time curve (AUC) for carbamazepine is about 80% to about 125% of the AUC for the oral maintenance dose.
34. The method of claim 25 , wherein the minimum carbamazepine plasma concentration is about 70% to about 130% of the minimum plasma concentration for the oral maintenance dose.
35. The method of claim 25 , wherein the minimum carbamazepine plasma concentration is about 80% to about 125% of the minimum plasma concentration for the oral maintenance dose.
36. A method of administering a carbamazepine sulfobutylether-7-β-cyclodextrin composition to a human having a seizure disorder comprising,
a) providing a carbamazepine sulfobutylether-7-β-cyclodextrin composition, wherein the composition comprises about 10 mg/mL carbamazepine and about 25% w/v sulfobutylether-7-β-cyclodextrin; and
b) intravenously administering the composition to said human, wherein the composition is administered as a replacement for oral carbamazepine in a dosage of about 65% to 75% of the human's oral dosage, wherein the area under plasma concentration-time curve (AUC) for carbamazepine is about 70% to about 130% of the AUC for the oral maintenance dose, the minimum carbamazepine plasma concentration is about 70% to about 130% of the minimum plasma concentration for the oral maintenance dose, and wherein trough carbamazepine concentrations remain within the therapeutic range.
37. The method of claim 36 , wherein the seizure disorder is selected from partial seizures with complex symptoms, generalized tonic-clonic seizures, mixed seizure patterns, epilepsy, status epilipticus and refractory seizure disorders.
38. The method of claim 37 , wherein the seizure disorder is epilepsy.
39. The method of claim 37 , wherein the seizure disorder is status epilipticus.
40. The method of claim 37 , wherein the seizure disorder is partial seizures with complex symptoms.
41. The method of claim 37 , wherein the seizure disorder is generalized tonic-clonic seizures.
42. The method of claim 37 , wherein the seizure disorder is mixed seizure patterns.
43. The method of claim 37 , wherein the seizure disorder is refractory seizure disorders.
44. A method of administering a carbamazepine sulfobutylether-7-β-cyclodextrin composition to a human having partial seizures with complex symptoms, generalized tonic-clonic seizures, or mixed seizure patterns comprising,
a) providing a carbamazepine sulfobutylether-7-β-cyclodextrin composition, wherein the composition comprises about 10 mg/mL carbamazepine and about 25% w/v sulfobutylether-7-β-cyclodextrin; and
b) intravenously administering the composition to said human, wherein the composition is administered as a replacement for oral carbamazepine in a daily dosage of about 65% to 75% of the human's daily oral dosage, and wherein administration occurs over a period from about 5 to about 60 minutes.
45. The method of claim 44 , wherein the human has partial seizures with complex symptoms.
46. The method of claim 44 , wherein the human has generalized tonic-clonic seizures.
47. The method of claim 44 , wherein the human has mixed seizure patterns.
48. The method of claim 44 , wherein administration occurs over a period of about 30 minutes.
49. The method of claim 44 , wherein administration occurs over a period of about 15 minutes.
50. The method of claim 44 , wherein administration occurs over a period of about 5 minutes.
51. The method of claim 44 , further comprising a dosing interval of about every 4-12 hours.
52. The method of claim 44 , wherein the carbamazepine sulfobutylether-7-β-cyclodextrin composition is administered in a daily dosage of about 70% of the human's daily oral dosage.
53. The method of claim 44 , wherein trough carbamazepine concentrations remain within the therapeutic range.
54. The method of claim 44 , wherein the area under plasma concentration-time curve (AUC) for carbamazepine is about 70% to about 130% of the AUC for the oral maintenance dose.
55. The method of claim 44 , wherein the area under plasma concentration-time curve (AUC) for carbamazepine is about 80% to about 125% of the AUC for the oral maintenance dose.
56. The method of claim 44 , wherein the minimum carbamazepine plasma concentration is about 70% to about 130% of the minimum plasma concentration for the oral maintenance dose.
57. The method of claim 44 , wherein the minimum carbamazepine plasma concentration is about 80% to about 125% of the minimum plasma concentration for the oral maintenance dose.