US 11,666,566 B2
Formulations and pharmacokinetics of deuterated benzoquinoline inhibitors of vesicular monoamine transporter 2
Andreas Sommer, Carlsbad, CA (US); Chengzhi Zhang, San Diego, CA (US); John Carter, Vista, CA (US); John Charles Arthur, Vista, CA (US); Margaret Bradbury, Vista, CA (US); Thomas George Gant, Carlsbad, CA (US); and Manouchehr Shahbaz, San Diego, CA (US)
Assigned to Auspex Pharmaceuticals, Inc., Parsippany, NJ (US)
Filed by AUSPEX PHARMACEUTICALS, INC., Parsippany, NJ (US)
Filed on Apr. 27, 2020, as Appl. No. 16/859,514.
Application 16/859,514 is a continuation of application No. 16/682,041, filed on Nov. 13, 2019, granted, now 11,033,540.
Application 16/682,041 is a continuation of application No. 16/163,380, filed on Oct. 17, 2018, abandoned.
Application 16/163,380 is a continuation of application No. 15/287,406, filed on Oct. 6, 2016, abandoned.
Application 15/287,406 is a continuation of application No. 15/044,655, filed on Feb. 16, 2016, granted, now 9,814,708, issued on Nov. 14, 2017.
Application 15/044,655 is a continuation of application No. 14/245,024, filed on Apr. 4, 2014, granted, now 9,296,739, issued on Mar. 29, 2016.
Application 14/245,024 is a continuation of application No. 14/030,322, filed on Sep. 18, 2013, granted, now 9,346,800, issued on May 24, 2016.
Claims priority of provisional application 61/702,586, filed on Sep. 18, 2012.
Prior Publication US 2020/0253952 A1, Aug. 13, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/20 (2006.01); A61K 9/28 (2006.01); A61K 47/38 (2006.01); A61P 25/14 (2006.01); A61K 31/473 (2006.01); A61K 9/00 (2006.01); A61K 9/16 (2006.01); A61K 9/48 (2006.01); A61K 9/50 (2006.01); A61K 31/4745 (2006.01); A61K 45/06 (2006.01); C07D 455/06 (2006.01)
CPC A61K 31/473 (2013.01) [A61K 9/0053 (2013.01); A61K 9/0065 (2013.01); A61K 9/1676 (2013.01); A61K 9/2013 (2013.01); A61K 9/2018 (2013.01); A61K 9/2027 (2013.01); A61K 9/2031 (2013.01); A61K 9/2054 (2013.01); A61K 9/2072 (2013.01); A61K 9/2077 (2013.01); A61K 9/2095 (2013.01); A61K 9/28 (2013.01); A61K 9/284 (2013.01); A61K 9/288 (2013.01); A61K 9/2846 (2013.01); A61K 9/2866 (2013.01); A61K 9/4808 (2013.01); A61K 9/5047 (2013.01); A61K 9/5073 (2013.01); A61K 9/5078 (2013.01); A61K 9/5084 (2013.01); A61K 31/4745 (2013.01); A61K 45/06 (2013.01); C07D 455/06 (2013.01); C07B 2200/05 (2013.01)] 18 Claims
 
1. A solid oral dosage form comprising 6 mg of d6-tetrabenazine and between about 5% and about 30% by weight of the dosage form of a sustained-release polymer comprising a poly(ethylene oxide) polymer or a hydroxypropyl methylcellulose (HPMC) polymer having a viscosity of less than 4,000 cPs,
wherein oral administration of the oral dosage form to a human results in a ratio of fed to fasted AUCinf of a total combined amount of deuterated dihydrotetrabenazine of >1 to 1.2; and
wherein oral administration of the oral dosage form to a human in a fed state, results in
an AUCinf in plasma of a total combined amount of deuterated dihydrotetrabenazine of about 132 hr*ng/mL; or
a Cmax in plasma of a total combined amount of deuterated dihydrotetrabenazine of about 15.5 ng/mL.