Methods of Treating alcoholism and alcohol related disorders using combination drug therapy and swellable polymers

1 . A method of treating a subject suffering from an alcohol related disorder comprising the step of orally administering to the stomach of a subject, a controlled release combination of an opioid antagonist and a GABA B agonist in a matrix wherein said matrix comprises a first polymeric matrix and a second polymeric matrix, and wherein the opioid antagonist is dispersed within the first polymeric matrix and the GABA B agonist is dispersed within the second polymeric matrix, said matrix being one that:

a) swells upon contact with water to promote retention of said oral drug dosage form in the stomach,

b) releases the opioid antagonist and the GABA B agonist into the gastric fluid by erosion of said first and second polymeric matrix by gastric fluid; and

c) exhibits different erosion rates for each of the first and second polymeric matrices.

2 . The method of claim 1 , wherein the opioid antagonist is selected from the group consisting of naltrexone, naloxone and nalmefene or a pharmaceutically acceptable salt, isomer, prodrug, analog, metabolite or derivative thereof.

3 . The method of claim 1 , wherein said opioid antagonist of the present invention is represented by the structure of the following formula:

R 1 is selected from the group consisting of hydrogen, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, or saturated or unsaturated heterocyclic group;

R 2 is selected from the group consisting of hydrogen, hydroxy, alkoxy, amino or substituted amino;

R 3 and R 4 are aliphatic;

R 3 and R 4 are taking together to form the following formula II:

R 5 and R 6 are both hydrogen or taken together R 5 and R 6 are ═O;

A, B and E are independently selected from hydrogen, halogen, R 1 , OR 1 , SR 1 , CONR 3 R 4 and NR 3 R 4 ; wherein R 3 and R 4 is independently selected from the group consisting of hydrogen, acyl, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, saturated or unsaturated heterocyclic group; or can be taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocyclic or heteroaromatic ring;

B and E are taken together to form the following formula III:

wherein Z is selected from O, S, or NR 1 ;

X and Y are independently selected from the group consisting of hydrogen, deuterium, halogen, nitrile, azide, R 1 , OR 1 , S(O) n R 1 , —NR 1 C(O)R 1 , —NR 1 C(O)NR 3 R 4 , —NR 1 S(O) n R 1 , —CONR 3 R 4 , and NR 3 R 4 ;

or X and Y, taken together with the carbon atom to which they are attached, are selected from the group consisting of CO, C═CHR 1 , C═NR 1 , C═NOR 1 , C═NO(CH 2 ) m R 1 , C═NNHR 1 , C═NNHCOR 1 , C═NNHCONR 1 R 2 , C═NNHS(O) n R 1 , or C═N—N═CHR 1 ;

R 2 and either X or Y taken together to form an additional sixth ring, which may be saturated or unsaturated;

L and M are independently selected from the group consisting of hydrogen, R 1 , OR 1 ;

or L and M, taken together with the carbon atom to which they are attached, is selected from the group consisting of C═CHR 1 , or a C 3 -C 10 spiro-fused carbocycle;

L and Y can be taken together to form a fused substituted or unsubstituted aryl or heteroaryl.

4 . The method of claim 1 , wherein said GABA B agonist is baclofen.