Method of administration of gamma hydroxybutyrate with monocarboxylate transporters

• US 9,050,302 B2
• Filed: 03/15/2013
• Issued: 06/09/2015
• Est. Priority Date: 03/01/2013
• Status: Active Grant

• Current Assignee: Jazz Pharmaceuticals Ireland Limited (Jazz Pharmaceuticals Plc)
• Original Assignee: Jazz Pharmaceuticals Ireland Limited (Jazz Pharmaceuticals Plc)
• Inventors: Eller, Mark
• Primary Examiner(s): Gembeh, Shirley V
• Application Number:
  US13/837,714
• Publication Number:
  US 20140249115A1
• Time in Patent Office: 816 Days
• Field of Search: 514/163, 514/557
• US Class Current: 1/1
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/33 Heterocyclic compounds
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients

Abstract

One embodiment of the present invention is to improve the safety and efficacy of the administration of GHB or a salt thereof to a patient. It has been discovered that the concomitant administration of an MCT inhibitor, such as diclofenac, valproate, or ibuprofen, will affect GHB administration. For example, it has been discovered that diclofenac lowers the effect of GHB in the body, thereby potentially causing an unsafe condition. Furthermore, it has been discovered that valproate increases the effect of GHB on the body, thereby potentially causing an unsafe condition.

Claims

1. A method for the treatment of cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy in a patient who is currently taking gamma-hydroxybutyrate (GHB) or a salt thereof comprising:

administering to the patient a dose of divalproex sodium concomitant to a dose of GHB or salt thereof; and

reducing the daily dosage amount of GHB or salt thereof administered to the patient by at least 20% wherein the daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is between 4.5 g to 9 g.

2. The method of claim 1 further comprising monitoring, patient response and adjusting the GHB dose to maintain the effect of the GHB.

3. The method of claim 1 wherein the daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 4.5 g.

4. The method of claim 3 wherein the daily dosage amount of GHB or salt thereof administered to the patient is reduced to lower than 3.6 g.

5. The method of claim 1 wherein the daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 6 g.

6. The method of claim 1 wherein the daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 7.5 g.

7. The method of claim 1 wherein the daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 9 g.

8. A method for the treatment of cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy in a patient who is currently taking gamma-hydroxybutyrate (GHB) or a salt thereof comprising:

reducing the daily dosage amount of GHB or salt thereof administered to the patient by at least 20% during concomitant administration of divalproex sodium, compared to the daily dosage amount of between 4.5 and 9 g of GHB or salt thereof currently used in the absence of concomitant administration of divalproex sodium.

9. The method of claim 8, wherein the daily dosage amount of GHB or salt thereof administered to the patient is reduced by at least 20% compared to the manufacturer'"'"'s, recommended daily dosage amount of GHB or salt thereof.

10. The method of claim 8 further comprising monitoring patient response and adjusting the GHB dose to maintain the effect of the GHB.

11. The method of claim 8 wherein the daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 4.5 g.

12. The method of claim 11 wherein the daily dosage amount of GHB or salt thereof administered to the patient is reduced to lower than 3.6 g.

13. A method for the treatment of cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy in a patient who is currently taking divalproex sodium comprising:

administering to the patient a starting daily dosage amount of gamma-hydroxybutyrate (GHB) or a salt thereof that is 20% lower than a manufacturer'"'"'s recommended starting daily dosage amount of between 4.5 and 9 g in the absence of concomitant administration of divalproex sodium.

14. The method of claim 13 wherein the starting daily dosage amount of GHB or salt thereof administered to the patient is lower than 4.5 g.

15. The method of claim 14 wherein the starting daily dosage amount of GHB or salt thereof administered to the patient is divided in two equal doses.

16. The method of claim 15 wherein the first dose of the two equal doses of GHB or salt thereof administered to the patient is lower than 2.25 g.

17. The method of claim 15 wherein the second dose of the two equal doses of GHB or salt thereof administered to the patient is lower than 2.25 g.

18. The method of claim 13 further comprising monitoring patient response and adjusting the GHB dose to treat the patient.

19. The method of claim 13 wherein the manufacturer'"'"'s recommended starting daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 4.5 g.

20. A method for the treatment of cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy in a patient who is currently taking divalproex sodium comprising:

administering to the patient a starting daily dosage amount of gamma-hydroxybutyrate (GHB) or a salt thereof that is 20% lower than the starting daily dosage amount of between 4.5 to 9 g GHB that would otherwise have been recommended to the patient if the patient was not currently taking divalproex sodium.

21. The method of claim 20 wherein the starting daily dosage amount of GHB or salt thereof administered to the patient who is currently taking divalproex sodium is lower than 4.5 g.

22. The method of claim 21 wherein the starting daily dosage amount of GHB or salt thereof administered to the patient who is currently taking divalproex sodium is divided in two equal doses.

23. The method of claim 22 wherein the first dose of the two equal doses of GHB or salt thereof administered to the patient is lower than 2.25 g.

24. The method of claim 23 wherein the second dose of the two equal doses of GHB or salt thereof administered to the patient is lower than 2.25 g.

25. The method of claim 20 further comprising monitoring patient response and adjusting the GHB dose to treat the patient.

26. The method of claim 20 wherein the starting daily dosage amount of GHB or salt thereof that would otherwise have been recommended to the patient if the patient was not currently taking divalproex sodium is 4.5 g.

27. A method for the treatment of cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy in a patient who is currently taking divalproex sodium comprising the steps of:

administering to the patient a daily dosage amount of gamma-hydroxybutyrate (GHB) or a salt thereof that is lower than 4.5 g.

28. The method of claim 27 wherein the daily dosage amount of GHB or salt thereof administered to the patient is divided in two equal doses.

29. The method of claim 28 wherein the first dose of the two equal doses of GHB or salt thereof administered to the patient is lower than 2.25 g.

30. The method of claim 28 wherein the second dose of the two equal doses of GHB or salt thereof administered to the patient is lower than 2.25 g.

31. A method for the treatment of cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy in a patient who is currently taking divalproex sodium comprising the steps of:

administering to the patient a dose of gamma-hydroxybutyrate (GHB) or a salt thereof that is lower than 2.25 g; and

administering to the patient a second dose of GHB or salt thereof that is lower than 2.25 g.