# US 10,864,181 B2 · Method of administration of gamma hydroxybutyrate with monocarboxylate transporters

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- Number: US 10,864,181 B2
- Document ID: US10864181B2
- Status: Granted
- Kind: B2
- Application number: 16/245,067
- Filed: 2019-01-10
- Published: 2019-09-12
- Granted: 2020-12-15
- Earliest claimed: 2013-03-01
- Assignees: Jazz Pharmaceuticals Ireland Limited
- Applicants: Jazz Pharmaceuticals Ireland Limited
- Inventors: Mark Eller
- Web page: https://patentgrep.com/patent/US10864181B2

## CPC

- A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60)
- A61K 31/20: having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K 31/33: Heterocyclic compounds
- A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/616: by carboxylic acids, e.g. acetylsalicylic acid
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 25/20: Hypnotics; Sedatives
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA

## 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

### Claim 1

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.

### Claim 2 (depends on 1)

The method of claim 1, wherein the PD interactions are measured by Cognitive Drug Research (CDR) system tasks or Karolinska Sleepiness Scale (K55).

### Claim 3 (depends on 2)

The method of claim 2, 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).

### Claim 4 (depends on 1)

The method of claim 1, 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).

### Claim 5 (depends on 4)

The method of claim 4, wherein the PK changes are measured by Cmax or AUC.

### Claim 6 (depends on 1)

The method of claim 1, further comprising monitoring the patient's response and adjusting the dose of GHB or salt thereof.

### Claim 7 (depends on 1)

The method of claim 1, 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.

### Claim 8 (depends on 1)

The method of claim 1, 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.

### Claim 9 (depends on 1)

The method of claim 1, 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.

### Claim 10 (depends on 1)

The method of claim 1, 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.

### Claim 11 (depends on 1)

The method of claim 1, wherein the daily dosage amount of GHB or salt thereof administered to the patient is reduced by about 15% to 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.

### Claim 12 (depends on 1)

The method of claim 1, wherein the patient is currently taking divalproex sodium.