# US 8,772,306 B1 · Method of administration of gamma hydroxybutyrate with monocarboxylate transporters

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- Number: US 8,772,306 B1
- Document ID: US8772306B1
- Status: Granted
- Kind: B1
- Application number: 13/872,997
- Filed: 2013-04-29
- Granted: 2014-07-08
- Earliest claimed: 2013-03-01
- Assignees: Jazz Pharmaceuticals, Inc.
- Applicants: Jazz Pharmaceuticals, Inc.
- Inventors: Mark Eller
- Web page: https://patentgrep.com/patent/US8772306B1

## 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 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 5% decrease in an effective dosage amount of the GHB or salt thereof when the patient is receiving a concomitant administration of valproate, an acid, salt, or mixture thereof.

### Claim 2 (depends on 1)

The method in accordance with claim 1, wherein there is at least about a 15% reduction in the effective dosage amount of the GHB or salt thereof given to the patient and wherein the valproate, acid, salt or mixture thereof is divalproex sodium.

### Claim 3 (depends on 2)

The method in accordance with claim 2, wherein the dose of the GHB or salt thereof given to the patient without concomitant administration of valproate, an acid, salt or mixture thereof is from 4.5 to 9 grams per day.

### Claim 4 (depends on 1)

The method in accordance with claim 1, wherein the effective dosage amount is a reduction 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.

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

The method in accordance with claim 1, further comprising administering aspirin to the patient.

### Claim 7 (depends on 1)

The method in accordance with claim 1, wherein the effective dosage amount of the GHB or a salt thereof is reduced from a range of 4.5 to 9 grams per day.

### Claim 8 (depends on 1)

The method in accordance with claim 1, wherein the dose of the GHB or salt thereof without concomitant administration of valproate, an acid, salt or mixture thereof is from 4.5 to 9 grams per day.

### Claim 9 (depends on 1)

The method in accordance with claim 1, wherein the effective dosage amount of the GHB or salt thereof is between 3 grams and 7 grams per day.

### Claim 10 (depends on 1)

The method in accordance with claim 1, wherein the effective dosage amount of the GHB or salt thereof is between 3.5 grams and 4 grams per day.

### Claim 11

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 valproate, an acid, salt or mixture thereof; and
orally administering a reduced amount of the GHB or salt thereof to the patient wherein the reduction is at least 5% compared to a dose without concomitant administration of valproate, an acid, salt or mixture thereof.

### Claim 12 (depends on 11)

The method in accordance with claim 11, wherein the amount of GHB or salt thereof is reduced at least 10% to 30%.

### Claim 13 (depends on 11)

The method in accordance with claim 11, wherein the amount of GHB or salt thereof is reduced at least 15% patient and wherein the valproate, acid, salt, or mixture thereof is divalproex sodium.

### Claim 14 (depends on 11)

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

### Claim 15 (depends on 11)

The method in accordance with claim 11, wherein the valproate, acid, salt or mixture thereof is administered within three days of administration of the GHB or salt thereof.

### Claim 16 (depends on 11)

The method in accordance with claim 11, wherein the patient is suffering from narcolepsy.

### Claim 17 (depends on 11)

The method in accordance with claim 11, further comprising administering aspirin to the patient.

### Claim 18 (depends on 11)

The method in accordance with claim 11, further comprising recommending to decrease the dose of GHB or salt thereof by 20% patient and wherein the valproate, acid, salt, or mixture thereof is divalproex sodium.

### Claim 19

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 starting 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 valproate, an acid, salt or mixture thereof;
warning of a potential drug/drug interaction due to the combination of valproate, an acid, salt or mixture thereof and the GHB salt; and
recommending reducing the dose of the GHB salt at least 15%.

### Claim 20 (depends on 19)

The method in accordance with claim 19, wherein the valproate, acid, salt or mixture thereof is administered within two weeks of administration of the GHB salt.

### Claim 21 (depends on 19)

The method in accordance with claim 19, wherein the valproate, acid, salt or mixture thereof is administered within three days of administration of the GHB salt.

### Claim 22 (depends on 19)

The method in accordance with claim 19, wherein the GHB salt is administered starting at a concentration of between 450 to 550 mg/ml.

### Claim 23 (depends on 22)

The method in accordance with claim 22, further comprising adding water to the GHB salt formulation.

### Claim 24 (depends on 19)

The method in accordance with claim 19, wherein the GHB salt formulation has a pH between 6.5 and 8.

### Claim 25 (depends on 19)

The method in accordance with claim 19, further comprising administering the reduced dose of the GHB salt to the patient.

### Claim 26 (depends on 19)

The method in accordance with claim 19, 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).

### Claim 27 (depends on 19)

The method in accordance with claim 19, further comprising administering aspirin to the patient.

### Claim 28 (depends on 19)

The method in accordance with claim 19, comprising recommending reducing a dose of GHB or salt thereof at least 20% patient and wherein the valproate, acid, salt, or mixture thereof is divalproex sodium.

### Claim 29 (depends on 19)

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

### Claim 30

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;
determining if the patient is also being administered valproate, an acid, salt or mixture thereof;
recommending a 20% decrease in the starting dose of the GHB salt such that a patient starts taking the GHB salt at an adjusted dosage amount between 3.5 grams and 4 grams the GHB salt per night administered orally.

### Claim 31 (depends on 30)

The method in accordance with claim 30, wherein the starting adjusted dosage amount of the GHB salt is about 3.6 grams.

### Claim 32 (depends on 30)

The method in accordance with claim 30, 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.

### Claim 33

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 valproate, an acid, salt or mixture thereof;
recommending a 20% decrease in the starting dose of the GHB salt such that the amount that the patient is administered is reduced to about 3.6 grams GHB per day.

### Claim 34 (depends on 33)

The method in accordance with claim 33, 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.