Compositions and methods for minimizing adverse drug experiences associated with oxybutynin therapy

• US 20050048107A1
• Filed: 12/08/2003
• Published: 03/03/2005
• Est. Priority Date: 04/26/2000
• Status: Active Grant

• Current Assignee: Allergan Sales LLC (Abbvie Incorporated)
• Original Assignee: Watson Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Sanders, Steven W., Ebert, Charles D.
• Granted Patent: US 7,081,250 B2
• Time in Patent Office: Days
• US Class Current: 424/449
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies

Abstract

The present invention provides compositions and methods for administering oxybutynin while minimizing the incidence and or severity of adverse drug experiences associated with oxybutynin therapy. In one aspect, these compositions and methods provide a lower plasma concentration of oxybutynin metabolites, such as N-desethyloxybutynin, which is presumed to be contributing at least in part to some of the adverse drug experiences, while maintaining sufficient oxybutynin plasma concentration to benefit a subject with oxybutynin therapy. The invention also provides isomers of oxybutynin and its metabolites that meet these characteristics of minimized incidence and/or severity of adverse drug experiences, and maintenance of beneficial and effective therapy for overactive bladder.

Claims

1. A method of treating with oxybutynin a human subject having overactive bladder, while minimizing an anticholinergic or antimuscarinic adverse drug experience associated with said oxybutynin treatment therapy comprising the step of:

administering as a transdermal patch, a composition comprising oxybutynin to said subject to provide a plasma area under the curve (AUC) ratio of oxybutynin to an oxybutynin metabolite of from about 0.5;

1 to about 5;

1, wherein the transdermal patch includes an effective amount of a permeation enhancer selected from the group consisting essentially of;

fatty acids, fatty acid esters, fatty alcohols, fatty acid esters of lactic acid or glycolic acid, glycerol di-and monoesters, short chain alcohols, and mixtures thereof.

2. The method of claim 1, wherein the AUC ratio of oxybutynin to an oxybutynin metabolite is from about 1:

1 to about 5;

1.

3. The method of claim 2, wherein the AUC ratio of oxybutynin to an oxybutynin metabolite is from about 0.8:

1 to about 1.5;

1.

4. The method of claim 1, wherein the metabolite of oxybutynin is N-desethyloxybutynin.

5. The method of claim 4, wherein the N-desethyloxybutynin is (R)-N-desethyloxybutynin, (S)-N-desethyloxybutynin or a combination thereof.

6. The method of claim 1, wherein the oxybutynin is a mixture of R-oxybutynin and S-oxybutynin.

7. The method of claim 6, wherein the oxybutynin is R-oxybutynin.

8. The method of claim 1, wherein the enhancer is a fatty acid.

9. The method of claim 1, wherein the enhancer is a fatty acid ester.

10. The method of claim 1, wherein the enhancer is a fatty alcohol.

11. The method of claim 1, wherein the enhancer is a short chain alcohol.

12. The method of 1, wherein the enhancer is a glycerol monoester.

13. An article of manufacture for transdermal application comprising:

a transdermal patch including a composition of oxybutynin and an effective amount of a permeation enhancer selected from the group consisting essentially of;

fatty acids, fatty acid esters, fatty alcohols, fatty acid esters of lactic acid or glycolic acid, glycerol di- and monoesters, short chain alcohols, and mixtures thereof, for administration to a human subject, wherein the patch provides, upon administration to said subject, a plasma AUC ratio of oxybutynin to an oxybutynin metabolite from about 0.5;

1 to about 5;

1, and wherein said patch minimizes an anticholinergic or antimuscarinic adverse drug experience associated with the administration of oxybutynin.

14. The article of manufacture of claim 13, wherein the AUC ratio of oxybutynin to an oxybutynin metabolite is from about 1:

1 to about 5;

1.

15. The article of manufacture of claim 14, wherein the AUC ratio of oxybutynin to an oxybutynin metabolite is from about 0.8:

1 to about 1.5;

1.

16. The article of manufacture of claims 13, wherein the metabolite of oxybutynin is N-desethyloxybutynin.

17. The article of manufacture of claim 16, wherein the N-desethyloxybutynin is (R)-N-desethyloxybutynin, (S)-N-desethyloxybutynin or a combination thereof.

18. The article of manufacture of claim 13, wherein the oxybutynin is a mixture of R-oxybutynin and S-oxybutynin.

19. The article of manufacture of claim 18, wherein the oxybutynin is R-oxybutynin.

20. The article of manufacture of claim 13, wherein the enhancer is a fatty acid.

21. The article of manufacture of claim 13, wherein the enhancer is a fatty acid ester.

22. The article of manufacture of claim 13, wherein the enhancer is a fatty alcohol.

23. The article of manufacture of claim 13, wherein the enhancer is a short chain alcohol.

24. The article of manufacture of claim 13, wherein the enhancer is a glycerol monoester.