Method of administration of gamma hydroxybutyrate with monocarboxylate transporters

• US 10,213,400 B2
• Filed: 01/12/2018
• Issued: 02/26/2019
• 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:
  US15/869,792
• Publication Number:
  US 20180200210A1
• Time in Patent Office: 410 Days
• Field of Search: 5141883
• 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 reducing adverse effects caused by a combination of gamma-hydroxybutyrate (GHB) or a salt thereof and divalproex sodium in a patient comprising:

administering a reduced daily dosage amount of GHB or a salt thereof to the patient of between about 5% to about 35%, compared to a daily dosage amount of GHB or salt thereof administered to the patient in the absence of concomitant administration of divalproex sodium;

wherein the patient is concomitantly administered divalproex sodium;

wherein the patient is a patient suffering from cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy and currently taking GHB or salt thereof;

wherein the daily dosage amount of GHB or salt thereof administered to the patient 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 the patient'"'"'s response and adjusting the dose of GHB or salt thereof.

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 1 wherein the daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 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 7.5 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 9 g.

7. The method of claim 1 wherein the daily dosage amount of GHB or salt thereof administered to the patient is reduced by between about 20% and about 35%.

8. A method for reducing adverse effects caused by combination of gamma-hydroxybutyrate (GHB) or salt thereof and divalproex sodium in a patient comprising:

administering a reduced daily dosage amount of GHB or salt thereof to the patient of between about 5% to and about 35%, compared to a manufacturer'"'"'s recommended starting daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium;

wherein the patient is concomitantly administered divalproex sodium;

wherein the patient is a patient suffering from cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy and currently taking GHB or salt thereof;

wherein the manufacturer'"'"'s recommended starting 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.

9. The method of claim 8 further comprising monitoring the patient'"'"'s response and adjusting the dose of GHB or salt thereof.

10. The method of claim 8 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.

11. The method of claim 8 wherein the manufacturer'"'"'s recommended starting daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is divided into two equal doses.

12. The method of claim 11 wherein a first or second dose of the two equal doses of GHB or salt thereof administered to the patient is lower than 2.25 g.

13. The method of claim 8 wherein the daily dosage amount of GHB or salt thereof administered to the patient is reduced by between about 20% and about 35%, compared to manufacturer'"'"'s recommended starting daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium.

14. 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.

15. A method for reducing adverse effects caused by combination of gamma-hydroxybutyrate (GHB) or salt thereof and divalproex sodium in a patient comprising:

administering to the patient a daily dosage amount of GHB or a salt thereof that is between about 5% and about 35% lower than a starting dosage amount of GHB or a salt thereof that would otherwise have been recommended to the patient if the patient was not currently taking divalproex sodium;

wherein the patient is concomitantly administered divalproex sodium;

wherein the patient is a patient suffering from cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy and currently taking GHB or salt thereof;

wherein the starting daily dosage amount of GHB or salt hereof is between 4.5 g and 9 g.

16. The method of claim 15 further comprising monitoring the patient'"'"'s response and adjusting the dose of GHB or salt thereof.

17. The method of claim 15 wherein the daily dosage amount of GHB or a salt thereof administered to the patient who is currently taking divalproex sodium is lower than 4.5 g.

18. The method of claim 15 wherein the daily dosage amount of GHB or a salt thereof administered to the patient who is currently taking divalproex sodium is divided into two equal doses.

19. The method of claim 18 wherein a first or second dose of the two equal doses of GHB or salt thereof administered to the patient is lower than 2.25 g.

20. The method of claim 15 wherein the starting daily dosage amount of GHB or a salt thereof is reduced by between about 20% and about 35%.