Claims for Patent: 11,986,446

Summary for Patent: 11,986,446

Title:	Method of administration of gamma hydroxybutyrate with monocarboxylate transporters
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.
Inventor(s):	Mark Eller
Assignee:	Jazz Pharmaceuticals Ireland Ltd
Application Number:	US17/562,787
Patent Claims:	1. A method for the treatment of a patient suffering from cataplexy in narcolepsy or excessive daytime sleepiness, the method comprising: administering a reduced daily dosage amount of gamma-hydroxybutyrate (GHB), a prodrug, or a salt thereof, to the patient; wherein the patient is concomitantly administered divalproex sodium; wherein the daily dosage amount of GHB, prodrug, or salt thereof, is reduced to compensate for pharmacokinetic (PK) and/or pharmacodynamic (PD) changes caused by the concomitant administration of divalproex sodium. 2. The method of claim 1, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is between 4.5 g to 9.0 g. 3. The method of claim 1 or 2, wherein a reduced daily dosage amount of a GHB prodrug is administered. 4. The method of any one of claims 1-3, wherein the GHB prodrug is gamma butyrolactone (GBL). 5. The method of claim 1, wherein the PD changes are measured by Cognitive Drug Research (CDR) system tasks or a Karolinska Sleepiness Scale (K55). 6. 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). 7. The method of claim 6, wherein the PK changes are measured by Cmax or AUC. 8. The method of claim 1, further comprising monitoring the patient's response and adjusting the dose of GHB, prodrug, or salt thereof. 9. The method of claim 1, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is 4.5 g. 10. The method of claim 1, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is 6 g. 11. The method of claim 1, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is 7.5 g. 12. The method of claim 1, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is 9 g. 13. The method of claim 1, wherein the daily dosage amount of GHB, prodrug, or salt thereof administered to the patient is reduced by about 15% to about 30%, compared to the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium. 14. The method of claim 1, wherein the daily dosage amount of GHB, prodrug, or salt thereof administered to the patient is reduced by about 20%, compared to the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium. 15. The method of claim 1, wherein the patient is currently taking divalproex sodium. 16. The method of claim 1, wherein the patient is suffering from excessive daytime sleepiness. 17. A method for the treatment of a patient comprising: administering a reduced daily dosage amount of gamma-hydroxybutyrate (GHB), a prodrug, or a salt thereof, to the patient; wherein the patient is concomitantly administered divalproex sodium; wherein the daily dosage amount of GHB, prodrug, or salt thereof, is reduced to compensate for pharmacokinetic (PK) and/or pharamacodynamic (PD) changes caused by the concomitant administration of divalproex sodium. 18. The method of claim 17, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is between 4.5 to 9.0 g. 19. The method of claim 17 or 18, wherein a reduced daily dosage amount of GHB prodrug is administered. 20. The method of any one of claims 17-19 , wherein the GHB prodrug is gamma butyrolactone (GBL). 21. The method of claim 17, wherein the PD changes are measured by Cognitive Drug Research (CDR) system tasks or a Karolinska Sleepiness Scale (K55). 22. The method of claim 17, wherein the PK chan ges 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). 23. The method of claim 22, wherein the PK changes are measured by Cmax or AUC. 24. The method of claim 17, further conprising monitoring the patient's response and adjusting the dose of GHB, prodrug, or salt thereof. 25. the method of claim 17, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is 4.5 g. 26. The method of claim 17, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is 6 g. 27. The method of claim 17, wherein the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium is 7.5 g. 28. The method of claim 17, wherein the daily dosage amount of GHB, prodrug, or salt thereof in absence of concomitant administration of divalproex sodium is 9 g. 29. The method of claim 17, wherein the daily dosage amount of GHB, prodrug, or salt thereof administered to the patient is reduced by about 15% to about 30%, compared to the daily dosage amoutn of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium. 30. The method of claim 17, wherein the daily dosage amount of GHB, prodrug, or salt thereof administered to the patient is reduced by about 20%, compared to the daily dosage amount of GHB, prodrug, or salt thereof in the absence of concomitant administration of divalproex sodium. 31. The method of claim 17, wherein the patient is currently taking divalproex sodium.