ORAL ADMINISTRATION OF PERIPHERALLY-ACTING OPIOID ANTAGONISTS

• US 20110160239A1
• Filed: 05/07/2009
• Published: 06/30/2011
• Est. Priority Date: 05/07/2008
• Status: Abandoned Application

• Current Assignee: Nektar Therapeutics
• Original Assignee: Nektar Therapeutics
• Inventors: Brodbeck, Kevin J., Kugler, Alan R.
• Application Number:
  US12/991,229
• Publication Number:
  US 20110160239A1
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

Peripherally-acting opioid antagonists can be orally administered to treat the side effects of opioid administration in convenient dosing schedules.

Claims

1. A method comprising orally administering to an individual a therapeutically effective dose of a peripherally acting opioid antagonist no more than twice daily.

2. The method of claim 1, used in the treatment of an individual suffering from one or more peripherially mediated opioid-induced side effects.

3. The method of claim 1, used in the treatment of an individual suffering from opioid-induced bowel dysfunction.

4. The method of claim 1, used in the treatment of an individual suffering from opioid-induced constipation.

5. The method of claim 1, used in the prevention of one or more peripherially mediated opioid-induced side effects.

6. The method of claim 5, wherein a therapeutically effective dose of an opioid is administered to the individual within 24 hours of administering to the individual a therapeutically effective dose of a peripherally acting opioid antagonist.

7. The method of claim 1, wherein the peripherally acting opioid antagonist is administered once a day.

8. The method of claim 1, wherein the peripherally acting opioid antagonist is administered twice a day.

9. The method of claim 1, wherein the total daily dose of the peripherally acting opioid antagonist is from 10 mg to 100 mg.

10. The method of claim 9, wherein the total daily dose of the peripherally acting opioid antagonist is from 25 mg to 100 mg.

11. The method of claim 1, wherein the therapeutically effective dose of the peripherally acting opioid antagonist is from 5 mg to 50 mg.

12. The method of claim 1, wherein the therapeutically effective dose provides a therapeutic benefit for at least ten hours each day.

13. The method of claim 1, wherein the therapeutic benefit is selected from the group consisting of the prevention of an opioid-induced side effect in an individual and the treatment of an individual suffering from an opioid-induced side effect.

14. The method of claim 1, wherein the peripherally acting opioid antagonist has the following formula:

15. The method of claim 1, wherein the opioid is selected from the group consisting of 1-α

-acetylmethadol, alfentanil, alphaprodine, anileridine, bremazocine, buprenorphine, butorphanol, codeine, cyclazocine, dezocine, diacetylmorphine, dihydrocodeine, ethylmorphine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, methotrimeprazine, morphine, nalbuphine, nefopam, normophine, noscapine, oxycodone, oxymorphone, papaverine, pentazocine, pethidine, phenazocine, propiram, propoxyphene, sufentanil, thebaine, tramadol and pharmaceutically acceptable salts of each of the foregoing.

16. A method comprising the steps of:

(i) administering to an individual a therapeutically effective amount of an opioid to provide a central analgesic effect;

(ii) orally administering, before, simultaneously with, or after step (i), to the individual a therapeutically effective amount of a peripherally acting opioid antagonist, wherein said dose of the peripherally acting opioid antagonist;

(a) provides a therapeutic benefit for at least ten hours; and

(b) does not cause significant inhibition of the central analgesic effect.

17. A unit dose form comprising a dose of an orally administrable opioid antagonist sufficient that, upon administration to an individual, provides a therapeutic benefit for at least 10 hours.

18. The unit dose form of claim 17, wherein the individual is experiencing a central analgesic effect.

19. The unit dose form of claim 18, wherein the unit dose form further comprises a therapeutically effective dose of an opioid.

20. The unit dose form of claim 17, wherein the individual is not experiencing a central analgesic effect.

21. The unit dose form of claim 17, wherein the therapeutic benefit is the treatment or prevention in an individual of opioid-induced side effect.

22. An orally administrable, peripherially acting opioid antagonist having a half-life in humans of greater than 10 hours.

23. A method comprising orally administering to an individual a therapeutically effective dose of a peripherally acting opioid antagonist, wherein said method induces a bowel movement in an individual receiving opioid therapy and suffering from opioid-induced constipation without significant inhibition of the central analgesic effect of the opioid in said individual.

24. A method comprising orally administering to an individual a therapeutically effective dose of a peripherally acting opioid antagonist, wherein said peripherally acting opioid antagonist reaches its Cmax in said individual within 3 hours of said administering.

25. A method comprising orally administering to an individual a therapeutically effective dose of a peripherally acting opioid antagonist, wherein said peripherally acting opioid antagonist provides an area under the curve from 0 to 12 hours following the administration in the range of 140 hours×

ng/mL to 1300 hours×

ng/mL.