Claims for Patent: 6,818,229

Summary for Patent: 6,818,229

Title:	Intermediate release nicotinic acid compositions for treating hyperlipidemia
Abstract:	Intermediate release nicotinic acid formulations having unique biopharmaceutical characteristics, such as Cmax, Tmax and AUC, which are suitable for oral administration once per day during the evening or at night for treating hyperlipidemia without causing drug-induced hepatotoxicity to such a level that requires the therapy to be discontinued, are disclosed. The intermediate nicotinic acid formulations can be administered as tablets in dosage strengths of, for example, 375 mg, 500 mg, 750 mg and 1000 mg.
Inventor(s):	Cefali; Eugenio A. (Fort Lauderdale, FL), Bova; David J. (Boca Raton, FL)
Assignee:	KOS Pharmaceuticals, Inc. (Miami, FL)
Application Number:	08/962,027
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,818,229
Patent Claims:	1. An intermediate release nicotinic acid formulation suitable for oral administration once-a-day for treating hyperlipidemia without causing drug-induced hepatotoixicity to a level which woud require use of said intermediate release nicotinic acid formulation to be discontinued, said intermediate release nicotinic acid formulation containing at least about 375 mg of nicotinic acid and having: a nicotinic acid Cmax of about 3 .mu.g/ml; a nicotinic acid Tmax in the range of between about 5.6 hours and about 6 bours; and an AUC for nictoinic acid of about 6 .mu.ghr/ml. 2. An intermediate release nicotinic acid formulation of claim 1, wherein said nicotinic acid formulation is a tablet. 3. An intermediate release nicotinic acid formulation suitable for oral administration once-a-day for treating hyperlipidemia without causing drug-induced hepatotoxicity to a level which would require use of said intermediate realse nicotinic acid formulation to be discontinued, said intermediate release nicotinic acid formulation containing at least about 375 mg of nicotinic acid and having: a nicotinuric acid Cmax of about 2 .mu.g/ml; a nicotinuric acid Tmax in the range of between about 5.6 hours and about 6 hours; and an AUC for nictoinuric acid of about 10 .mu.ghr/ml. 4. An intermediate release nicotinic acid formulation of clain 3, wherein said nicotinic acid formulation is a tablet. 5. An intermediate release nicotinic acid formulation suitable for oral administration once-a-day for treating hyperlipidemia without causing drug-induced hepatotoxicity to a level which would require use of said intermediate release nicotinc acid fomlation to be discontinued, said intermediate release nicotinic acid formulation containing at least about 500 mg of nicotinic acid and having: a nicotinic acid Cmax in the range of from between about 1 .mu.g/ml and 10 .mu.g/ml; a nicotinic acid Tmax in the range of between about 5.6 hours and about 6 hours; and an AUC for nictoinic acid in the range of from between about 2 .mu.ghr/ml and about 34 .mu.ghr/ml. 6. An intermediate release nicotnic acid formulation of claim 5, wherein the Cmax has a mean of about 4 .mu.g/ml and the AUC has a mean of about 9 .mu.ghr/ml. 7. An intermediate release nicotinic acid formulation of claim 5, wherein said nicotinic acid formulation is a tablet. 8. An intermediate release nicotinic acid formulation of claim 6, wherein said nicotinic acid formulation is a tablet. 9. An intermediate release nicotinic acid formulation suitable for oral admministration once-a-day for treating hyperlipidemia without causing drug-induced hepatotoxicity to a level which would require use of said intermediate release nicotinic acid formulation to be discontinued, said intermediate release nicotinic acid formulation containig at least about 500 mg of nicotinic acid and having: a nicotinuric acid Cmax in the range of from between about 2 .mu.g/ml and 3 .mu.g/ml; a nicotinuric acid Tmax in the range of beween about 5.6 hours and about 6 hours; and an AUC for nicotinuric acid in the range of from between about 6 .mu.ghr/ml and about 16 .mu.ghr/ml. 10. An intermediate release nicotinic acid formulation of claim 9, wherein the Cmax has a mean of about 2 .mu.g/ml and the AUC has a mean of about 9 .mu.ghr/ml. 11. An intermediate release nicotinic acid formulation of claim 9, wherein said nicotinic acid formulation is a tablet. 12. An intermediate release nicotinic acid formulation of claim 10, wherein said nicotnic acid formulation is a tablet. 13. An intermediate release nicotinic acid formulation suitable for oral asministration once-a-day for treating hyperlipidemia without causing drug-induced hepatotoxcity to a level which would require use of said intermediate release nicotinic acid formlation to be discontinued, said intermediate release nicotinic acid formulation containing at least about 750 mg of nicotinic acid and having: a nicotinic acid Cmax in the range of from between about 8 .mu.g/ml and 9 .mu.g/ml; a nicotinic acid Tmax in the range of between about 5.6 hours and about 6 hours; and an AUC for nictoinic acid in the range of from between about 21 .mu.ghr/ml and about 22 .mu.ghr/ml. 14. An intermediate release nicotinic acid formulation of claim 13, wherein the Cmax has a mean of about 8 .mu.g/ml and the AUC has a mean of about 21 .mu.ghr/ml. 15. An intermediate release nicotinic acid formulation of claim 13, wherein said nicotinic acid formulation is a tablet. 16. An intermediate release nicotinic acid formulation of claim 14, wherein said nicotinic acid formulation is a tablet. 17. An intermediate release nicotinic acid formulation suitable for oral administration once-a-day for treating hyperlipidemia without causing drug-induced hepatotoxicity to a level which would require use of said intermediate release nicotinic acid formulation to be discontinued, said intermediate release nicotinic acid formulation containing at least about 750 mg of nicotinic acid and having: a nicotinuric acid Cmax in the range of from between about 3 .mu.g/ml and 3.2 .mu.g/ml; a nicotinuric acid Tmax in the range of between about 5.6 hours and about 6 hours; and an AUC for nicotinuric acid in the range of from between about 11 .mu.ghr/ml and about 13 .mu.ghr/ml. 18. An intermediate release nocotinic acid formulation of claim 17, wherein the Cmax has a mean of about 3 .mu.g/ml and the AUC his a mean of about 12 .mu.ghr/ml. 19. An intermediate release nicotinic acid formulation of claim 17, wherein said nicotinic acid formulation is a tablet. 20. An intermediate release nicotinic acid formulation of claim 19, wherein said nicotinic acid formulation is a tablet. 21. An intermediate release nicotrinic acid formulation suitable for oral administration once-a-day for treating hyperlipidemia without causing drug-induced hepatotoxicity to a level which would require use of said intermediate release nicotinic acid formulation to be discontinued, said intermediate release nicotinic acid formulation containg at least about 100 mg of nicoinic acid and having: a nicotinic acid Cmax in the range of from between about 9 .mu.g/ml and 17 .mu.g/ml; a nicotinic acid Tmax in the range of between about 5.6 hours and bout 6 hours; and an AUC for nictoinic acid in the range of from between about 24 .mu.ghr/ml and about 43 .mu.ghr/ml. 22. An intermediate release nicotinic acid formulation of claim 21, wherein the Cmax has a mean of about 13 .mu.g/ml and the AUC has a mean of about 33 .mu.ghr/ml. 23. An intermediate release nicotinic acid formulation of claim 21, wherein said nicotinic acid formulation is a tablet. 24. An intermediate release nicotinic acid formulation of claim 22, wherein said nicotinic acid formuation is a tablet. 25. An intermediate release nicotinic acid formulation suitable for oral administration once-a-day for treating hyperlipidemia without causing drug-induced hepatotoxicity to a level which would require use of said intermediate release nicotinic acid formulation to be discontinued, said intermediate release nicotinic acid formulation containing at least about 1000 mg of nicotinic acid and having: a nicotinuric acid Cmax in the range of from between about 3 .mu.g/ml and 5 .mu.g/ml; a nicotinuric acid Tmax in the range of between about 5.6 hours and about 6 hours; and an AUC for niotinuric acid in the range of from between about 12 .mu.ghr/ml and about 19 .mu.ghr/ml. 26. An intermediate release nicotinic acid formulation of claim 25, wherein the Cmax has a mean of about 4 .mu.g/ml and the AUC has a mean of about 15 .mu.ghr/ml. 27. An intermediate release nicotinic acid formulation of claim 25, wherein said nicotinic acid formulation is a tablet. 28. An intermediate release nicotinic acid formulation of claim 26, wherein said nicotinic acid formulation is a tablet.