Compositions for drug administration
View Patent ↗The present invention provides compositions and methods and for increasing the bioavailability of therapeutic agents in a subject, as well as compositions and methods for providing migraine pain relief. The compositions include at least one alkyl glycoside and at least one therapeutic agent, such as a 5-HT receptor agonist, wherein the alkylglycoside has an alkyl chain length from about 10 to about 16 carbon atoms.
1. A composition comprising:
a) a therapeutically effective amount of a 5-HT receptor agonist, the 5-HT agonist being sumatriptan, naratriptan, rizatriptan, eletriptan, frovatriptan, almotriptan, zolmitriptan, salt thereof, or combination thereof; and
b) an alkylsaccharide having an alkyl chain including between 10 to 16 carbons, wherein the composition is formulated for intranasal administration, exhibits a Tmax of less than about 20 minutes, and exhibits a Cmax greater than 15 ng/mL.
2. The composition of claim 1 , wherein the alkylsaccharide concentration is about 0.05% to 2%.
3. The composition of claim 1 , wherein the alkylsaccharide is undecyl-beta-D-maltoside, dodecyl-beta-D-maltoside, tridecyl-beta-D-maltoside, tetradecyl-beta-D-maltoside, or combination thereof.
4. The composition of claim 1 , wherein the composition is formulated for administration into the circulatory system of a subject via the oral, ocular, intranasal, nasolacrimal, inhalation, pulmonary, sublingual, buccal, or CSF delivery route.
5. The composition of claim 1 , wherein the composition provides an AUC 0-1 hr for the 5-HT agonist of about 1.3 fold, 1.5 fold, or greater as compared to a corresponding AUC 0-1 hr provided in the absence of the alkylsaccharide.
6. The composition of claim 1 , wherein the composition provides a Cmax for the 5-HT agonist of about 1.3 fold or greater as compared to a corresponding Cmax provided in the absence of the alkylsaccharide.
7. The composition of claim 1 , wherein the composition provides a plasma or blood concentration of the 5-HT agonist at a time point of about 10-15 minutes following administration to a human at least about 1.3 fold, 1.5 fold, or higher as compared to a plasma or blood concentration of the agonist at a time point about 60 minutes following administration.
8. The composition of claim 1 , wherein the composition provides a maximum plasma or blood concentration of the 5-HT agonist at a time point of less than about 20 minutes following administration to a human that is at least about 1.3 fold, 1.5 fold, or higher as compared to a plasma or blood concentration of the antagonist at a time point about 60 minutes following administration.
9. The composition of claim 1 , wherein the composition provides a Cmax for the 5-HT agonist in plasma or blood within less than about 20 minutes following administration to a human wherein the alkylsaccharide concentration is 0.05 to 0.2%.
10. The composition of claim 1 , wherein the composition provides a Cmax for the 5-HT agonist in plasma or blood within less than about 20 minutes following administration to a human and a sustained 5-HT agonist concentration at 60 minutes that is at least about 0.25 times Cmax.
11. The composition of claim 1 , wherein the composition has a Cmax of at least about 17 ng/mL.
12. The composition of claim 1 , wherein the composition has a ratio of dose/Cmax of greater than about 1×10(exp 6) mL (exp−1) (1×10 6 mL −1 ).
13. The composition of claim 1 , wherein the composition has a ratio of dose/Cmax of at least about 1.15×10(exp 6) mL (exp−1) (1.15×10 6 mL −1 ).
14. The composition of claim 1 , wherein the composition has a Tmax of less than about 15 minutes.
15. The composition of claim 1 , wherein the 5-HT receptor agonist concentration is between 5 mg and 100 mg.
16. The composition of claim 1 , wherein the composition provides an AUC0-1 hr that is greater than about 10 ng*hr/mL.
17. The composition of claim 1 , wherein the 5-HT receptor agonist is sumatriptan and the composition provides an a plasma blood level of sumatriptan greater than or equal to about 5 ng/mL in about 5 minutes or less.
18. The composition of claim 1 , wherein the composition comprises about 20 mg of sumatriptan and provides a plasma blood level of sumatriptan greater than or equal to about 16 ng/mL in about 20 minutes or less.
19. The composition of claim 1 , wherein the 5-HT receptor agonist is sumatriptan and the composition provides a plasma blood level of sumatriptan greater than or equal to about 5 ng/mL in about 2 minutes or less.
20. The composition of claim 1 , wherein the 5-HT receptor agonist is sumatriptan and the composition provides a plasma blood level of sumatriptan greater than or equal to about 10 ng/mL in about 15 minutes or less.