MODIFIED RELEASE GAMMA- HYDROXYBUTYRATE FORMULATIONS HAVING IMPROVED PHARMACOKINETICS
Modified release formulations of gamma-hydroxybutyrate having improved dissolution and pharmacokinetic properties are provided, and therapeutic uses thereof.
1 . A method of treating a disorder treatable with a pharmaceutically acceptable salt of gamma-hydroxybutyrate in a human subject in need thereof, the method comprising:
orally administering a single nighttime daily dose to said human,
wherein said single nighttime daily dose comprises a first salt of gamma-hydroxybutyric acid and a second salt of gamma-hydroxybutyric acid,
wherein the first salt is selected from the group consisting of a sodium salt of gamma-hydroxybutyric acid, a calcium salt of gamma-hydroxybutyric acid, a potassium salt of gamma-hydroxybutyric acid, and a magnesium salt of gamma-hydroxybutyric acid,
wherein the second salt differs from the first salt and is selected from the group consisting of a sodium salt of gamma-hydroxybutyric acid, a calcium salt of gamma-hydroxybutyric acid, a potassium salt of gamma-hydroxybutyric acid, and a magnesium salt of gamma-hydroxybutyric acid, and
wherein the orally administering occurs only once nightly; and
concomitantly administering divalproex sodium.
2 . The method of claim 1 , wherein the human subject achieves a decrease in excessive daytime sleepiness when measured by the Epworth Sleepiness Scale (ESS).
3 . The method of claim 1 , wherein the human subject achieves a decrease in excessive daytime sleepiness when measured by the Maintenance of Wakefulness Test.
4 . The method of claim 1 , wherein the human subject achieves an improved Clinical Global Impression (CGI) rating of sleepiness.
5 . The method of claim 1 , wherein the human subject achieves a decrease in weekly cataplexy attacks.
6 . The method of claim 1 , wherein the disorder comprises cataplexy or excessive daytime sleepiness (EDS) in a patient with narcolepsy.
7 . The method of claim 1 , wherein the single nighttime daily dose comprises an immediate release portion and a modified release portion.
8 . The method of claim 7 , wherein the immediate release portion comprises calcium oxybate, potassium oxybate, and magnesium oxybate.
9 . The method of claim 1 , wherein the orally administering occurs with ¼ cup water.
10 . A method of treating a disorder treatable with a pharmaceutically acceptable salt of gamma-hydroxybutyrate in a human subject in need thereof, the method comprising:
initiating a starting dosage, wherein the initiating comprises orally administering a single nighttime daily dose to said human,
wherein said single nighttime daily dose comprises a sodium salt of gamma-hydroxybutyric acid, a calcium salt of gamma-hydroxybutyric acid, a potassium salt of gamma-hydroxybutyric acid, and a magnesium salt of gamma-hydroxybutyric acid,
wherein the orally administering occurs only once nightly; and
concomitantly administering divalproex sodium.
11 . The method of claim 10 , wherein the human subject achieves a decrease in excessive daytime sleepiness when measured by the Epworth Sleepiness Scale (ESS).
12 . The method of claim 10 , wherein the human subject achieves a decrease in excessive daytime sleepiness when measured by the Maintenance of Wakefulness Test.
13 . The method of claim 10 , wherein the human subject achieves an improved Clinical Global Impression (CGI) rating of sleepiness.
14 . The method of claim 10 , wherein the human subject achieves a decrease in weekly cataplexy attacks.
15 . The method of claim 10 , wherein the disorder comprises cataplexy or excessive daytime sleepiness (EDS) in a patient with narcolepsy.
16 . The method of claim 10 , wherein the single nighttime daily dose comprises an immediate release portion and a modified release portion.
17 . The method of claim 16 , wherein the immediate release portion comprises calcium oxybate, potassium oxybate, and magnesium oxybate.
18 . The method of claim 10 , wherein the orally administering occurs with ¼ cup water.
19 . A method of treating a disorder treatable with a pharmaceutically acceptable salt of gamma-hydroxybutyrate in a human subject in need thereof, the method comprising:
initiating a starting dosage, wherein the initiating comprises orally administering a single nighttime daily dose to said human,
wherein said single nighttime daily dose comprises a calcium salt of gamma-hydroxybutyric acid, a potassium salt of gamma-hydroxybutyric acid, and a magnesium salt of gamma-hydroxybutyric acid,
wherein the orally administering occurs only once nightly; and
concomitantly administering divalproex sodium.
20 . The method of claim 19 , wherein the human subject achieves a decrease in excessive daytime sleepiness when measured by the Epworth Sleepiness Scale (ESS).
21 . The method of claim 19 , wherein the human subject achieves a decrease in excessive daytime sleepiness when measured by the Maintenance of Wakefulness Test.
22 . The method of claim 19 , wherein the human subject achieves an improved Clinical Global Impression (CGI) rating of sleepiness.
23 . The method of claim 19 , wherein the human subject achieves a decrease in weekly cataplexy attacks.
24 . The method of claim 19 , wherein the disorder comprises cataplexy or excessive daytime sleepiness (EDS) in a patient with narcolepsy.
25 . The method of claim 19 , wherein the single nighttime daily dose comprises an immediate release portion and a modified release portion.
26 . The method of claim 19 , wherein the orally administering occurs with ¼ cup water.