METHOD OF ADMINISTRATION OF GAMMA HYDROXYBUTYRATE WITH MONOCARBOXYLATE TRANSPORTERS

• US 20190274980A1
• Filed: 01/10/2019
• Published: 09/12/2019
• 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
• Granted Patent: US 10,864,181 B2
• Time in Patent Office: Days
• 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

1-26. -26. (canceled)

27. A method for the treatment of cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy in a patient, the method comprising:

administering a reduced daily dosage amount of gamma-hydroxybutyrate (GHB) or a salt thereof to a patient who is concomitantly administered divalproex sodium;

wherein the patient is suffering from cataplexy in narcolepsy or excessive daytime sleepiness in narcolepsy;

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; and

wherein the reduced daily dosage amount of GHB or salt thereof compensates for pharmacokinetic (PK) and/or pharmacodynamic (PD) changes caused by the divalproex sodium.

28. The method of claim 27, wherein the PD interactions are measured by Cognitive Drug Research (CDR) system tasks or Karolinska Sleepiness Scale (KSS).

29. The method of claim 28, wherein the CDR system tasks are selected from the group consisting of Simple Reaction Time (SRT), Digit Vigilance (DV), Choice Reaction time (CRT), tracking distance from target, and Numeric Working Memory (NWM).

30. The method of claim 27, wherein the PK changes are measured by one or more parameters selected from the group consisting of plasma concentration, Cmax, Cn, C24, Tmax, and Area Under the Curve (AUC).

31. The method of claim 30, wherein the PK changes are measured by Cmax or AUC.

32. The method of claim 27, further comprising monitoring the patient'"'"'s response and adjusting the dose of GHB or salt thereof.

33. The method of claim 27, 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.

34. The method of claim 27, wherein the manufacturer'"'"'s recommended starting daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 6 g.

35. The method of claim 27, wherein the manufacturer'"'"'s recommended starting daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 7.5 g.

36. The method of claim 27, wherein the manufacturer'"'"'s recommended starting daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium is 9 g.

37. The method of claim 27, wherein the daily dosage amount of GHB or salt thereof administered to the patient is reduced by between about 15% and about 30%, compared to manufacturer'"'"'s recommended starting daily dosage amount of GHB or salt thereof in the absence of concomitant administration of divalproex sodium.

38. The method of claim 27, wherein the patient is currently taking divalproex sodium.