Method of administration of gamma hydroxybutyrate with monocarboxylate transporters

• US 8,952,029 B2
• Filed: 04/29/2013
• Issued: 02/10/2015
• 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:
  US13/873,000
• Publication Number:
  US 20140249222A1
• Time in Patent Office: 652 Days
• Field of Search: 514/188.3
• US Class Current: 514/275
• 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 treating a patient who is suffering from excessive daytime sleepiness, cataplexy, sleep paralysis, apnea, narcolepsy, sleep time disturbances, hypnagogic hallucinations, sleep arousal, insomnia, or nocturnal myoclonus with gamma-hydroxybutyrate (GHB) or a salt thereof, said method comprising:

orally administering to the patient in need of treatment at least a 5% increase in an effective dosage amount between 1 gram and 10 grams per day of the GHB or salt thereof when the patient is receiving a concomitant administration of diclofenac or a salt thereof.

2. The method in accordance with claim 1, wherein there is at least about a 15% increase in the effective dosage amount of the GHB or salt thereof normally given to the patient.

3. The method in accordance with claim 2, wherein the dose of GHB or salt thereof given to the patient without concomitant administration of diclofenac is a range between 4.5 to 9 grams per day.

4. The method in accordance with claim 1, wherein the effective dosage amount is increased between the range of about 5% to 10%, about 10% to 15%, about 15% to 20%, about 20% to 25%, about 25% to 30%, about 30% to 35%, about 35% to 40%, about 40% to 45%, or about 45% to 50%, relative to the dose of the GHB or salt thereof normally given to the patient.

5. The method in accordance with claim 1, wherein the patient is suffering from narcolepsy.

6. The method in accordance with claim 1, wherein the effective dosage amount is increased from a range of between 4.5 to 9 grams per day.

7. The method in accordance with claim 1, wherein the amount of GHB or salt thereof administered to the patient is between 7 grams and 12 grams per day after the increase.

8. The method in accordance with claim 1, wherein the amount of GHB or salt thereof administered to the patient is between 9 grams and 11 grams per day after the increase.

9. A method of safely administering GHB or a salt thereof for excessive daytime sleepiness, cataplexy, sleep paralysis, apnea, narcolepsy, sleep time disturbances, hypnagogic hallucinations, sleep arousal, insomnia, or nocturnal myoclonus in a human patient who is being administered GHB, said method comprising:

determining if the patient has taken, or will take, a concomitant dose of diclofenac or a salt thereof; and

orally administering an increased amount of the GHB or salt thereof to the patient wherein the increase is at least 5% compared to a dose without concomitant administration of diclofenac or salt thereof that is between 1 gram and 10 grams per day.

10. The method in accordance with claim 9, wherein the amount of GHB or salt thereof administered to the patient is increased at least 15%.

11. The method in accordance with claim 9, wherein the diclofenac or salt thereof is administered within two weeks of administration of the GHB or salt thereof.

12. The method in accordance with claim 9, wherein the diclofenac or salt thereof is administered within three days of administration of the GHB or salt thereof.

13. The method in accordance with claim 9, wherein the patient is suffering from narcolepsy.

14. The method in accordance with claim 9, further comprising recommending to increase the starting dose by 20%.

15. A method for treating a patient who is suffering from narcolepsy, said method comprising:

administering a therapeutically effective amount of a formulation containing a GHB salt to a patient at between 1 gram and 10 grams per day and at a concentration of between 350 and 750 mg/ml with a pH of between 6 and 10;

determining if the patient is also being administered diclofenac or a salt thereof;

warning of a potential drug/drug interaction due to the combination of diclofenac or a salt thereof and the GHB salt; and

recommending increasing the dose of the GHB salt at least 15%.

16. The method in accordance with claim 15, wherein the diclofenac or salt thereof is administered within two weeks of administration of the GHB salt.

17. The method in accordance with claim 15, wherein the diclofenac or a salt thereof is administered within three days of administration of the GHB salt.

18. The method in accordance with claim 15, wherein the GHB salt is administered at a concentration of between 450 to 550 mg/ml.

19. The method in accordance with claim 18, further comprising adding water to the GHB salt formulation.

20. The method in accordance with claim 15, wherein the GHB salt formulation has a pH between 6.5 and 8.

21. The method in accordance with claim 15, further comprising administering the increased dose of the GHB salt to the patient.

22. The method in accordance with claim 15, wherein the GHB salt comprises a single salt or a mixture of salts of GHB selected from the group consisting of a sodium salt of hydroxybutyrate (Na•

GHB), a potassium salt of gamma-hydroxybutyrate (K•

GHB), a magnesium salt of gamma-hydroxybutyrate (Mg•

(GHB)₂), and a calcium salt of gamma-hydroxybutyrate (Ca•

(GHB)₂).

23. The method in accordance with claim 15, wherein the dose of GHB or salt thereof without concomitant administration of diclofenac is a range between 4.5 to 9 grams per day.

24. The method in accordance with claim 15, comprising recommending increasing a starting dose at least 20%.

25. The method in accordance with claim 15, further comprising adding water to the GHB salt formulation.

26. The method in accordance with claim 15, further comprising optionally diluting the GHB salt formulation from a starting concentration of between 350 and 750 mg/ml with a pH of between 6 and 10.

27. A method for treating a patient who is suffering from narcolepsy, said method comprising:

orally administering a therapeutically effective amount of a formulation containing a GHB salt;

determining if the patient is also being administered diclofenac or salt thereof;

recommending a 20% increase in the starting dose of the GHB salt such that the amount that the patient is administered is increased to about 5.4 grams GHB per day.

28. The method in accordance with claim 27, further comprising optionally diluting the GHB salt formulation from a starting concentration of between 350 and 750 mg/ml with a pH of between 6 and 10.