Patent EA-002720-B1 (EA)
Title: Therapeutic formulation for administering tolterodine with controlled release and method for treating urinary bladder using thereof
Inventor: NILVEBRANT LISBETH
IPC: A61K/
Filed: 1999-08-26
Abstract: 1. A method of treating unstable or overactive urinary bladder, wherein the method comprises administering to a patient in need of such treatment tolterodine or a tolterodine-related compound, or a pharmaceutically acceptable salt thereof, in a pharmaceutically effective amount thereof through a controlled release formulation capable of maintaining a substantially constant serum level of the active moiety or moieties for at least 24 hours and having a mean fluctuation index of said serum level of active moiety or moieties that is not higher than about 2.0, said flutuation index, FI, being defined as FI = (Cmax - Cmin)/AUCτ/τ, wherein Cmax and Cmin are the maximum and minimum concentrations, respectively, of active moiety or moieties, AUCτ is the area under the serum concentration profile, and τ is the length of the dosage interval. 2. The method according to claim 1, wherein said a mean fluctuation index is not higher than about 1.0. 3. The method according to claim 1 or 2, wherein tolterodine, its 5-hydroxymethyl metabolite or the racemate corresponding to tolterodine is administered, and the 24-hour serum profile, expressed as the AUC of unbound tolterodine and 5-hydroxymethyl metabolite, is from about 5 to about 150 nMxh, preferably from about 10 nMxh to about 120 nMxh. 4. The method according to claim 1, 2 or 3, wherein tolterodine, its 5-hydroxymethyl metabolite or the racemate corresponding to tolterodine is administered, and the serum level of unbound tolterodine and 5-hydroxymethyl metabolite is in the range of about 0.2 to about 6.3 nM, preferably in the range of about 0.4 to about 5.0 nM. 5. The method according to any one of claims 1 to 4, wherein the controlled release formulation is a capsule or tablet for oral administration once daily. 6. The method according to any one of claims 1 to 4, wherein the controlled release formulation is a transdermal preparation, preferably a transdermal patch. 7. The method according to any one of claims 1 to 6, wherein tolterodine is administered. 8. The method according to any one of claims 1 to 6, wherein urinary incontinence is treated. 9. A pharmaceutical formulation containing tolterodine or a tolterodine-related compound, or a pharmaceutically acceptable salt thereof, which formulation when administered to a patient provides controlled release of tolterodine or said tolterodine-related compound, or salt thereof, such that a substantially constant serum level of the active moiety or moieties is maintained for at least 24 hours, a mean fluctuation index of said serum level of active moiety or moieties that is not higher than about 2.0, said flutuation index, FI, being defined as FI = (Cmax - Cmin)/AUCτ/τ, wherein Cmax and Cmin are the maximum and minimum concentrations, respectively, of active moiety or moieties, AUCτ is the area under the serum concentration profile, and τ is the length of the dosage interval. 10. The formulation according to claim 9, wherein said a mean fluctuation index is not higher than about 1.0. 11. The formulation according to claim 9 or 10, wherein tolterodine, its 5-hydroxymethyl metabolite or the racemate corresponding to tolterodine is administered, and the 24-hour serum profile, expressed as the AUC of unbound tolterodine and 5-hydroxymethyl metabolite, is from about 5 to about 150 nMxh, preferably from about 10 nMxh to about 120 nMxh. 12. The formulation according to claim 9 or 10, wherein tolterodine, its 5-hydroxymethyl metabolite or the racemate corresponding to tolterodine is administered, and the serum level of unbound tolterodine and 5-hydroxymethyl metabolite is in the range of about 0.2 to about 6.3 nM, preferably in the range of about 0.4 to about 5.0 nM. 13. The formulation according to any one of claims 9 to 12, which is a capsule or tablet for oral administration once daily. 14. The formulation according to any one of claims 1 to 12, which is a transdermal preparation, preferably a transdermal patch. 15. The formulation according to any one of claims 9 to 14, which provides controlled release of tolterodine. 16. Use of tolterodine or a tolterodine-related compound, or a pharmaceutically acceptable salt thereof, for the manufacture of a therapeutical formulation for treating unstable or overactive urinary bladder, which formulation provides controlled release of tolterodine or said tolterodine-related compound, or salt thereof, such that a substantially constant serum level of the active moiety or moieties is maintained for at least 24 hours, a mean fluctuation index of said serum level of active moiety or moieties that is not higher than about 2.0, said flutuation index, FI, being defined as FI = (Cmax - Cmin)/AUCτ/τ, wherein Cmax and Cmin are the maximum and minimum concentrations, respectively, of active moiety or moieties, AUCτ is the area under the serum concentration profile, and τ is the length of the dosage interval. 17. The use according to claim 16, wherein a formulation according to any one of claims 10 to 15 is manufactured.