Methods of administering an aripiprazole injectable preparation

Abstract

The present disclosure is directed to the methods of treating a patient with schizophrenia or bipolar I disorder by administering to the patient an injectable preparation of aripiprazole, wherein the patient is administered the injectable preparation about once every two months.

1 - 24 . (canceled) 
     
     
         25 . A method of treating a patient with schizophrenia or bipolar I disorder comprising:
 administering intramuscularly to the patient an injectable preparation comprising aripiprazole or a salt thereof wherein the patient is administered the injectable preparation about once every two months.   
     
     
         26 . The method according to  claim 25 , wherein the administration of the injectable preparation results in a total amount of aripiprazole ranging from about 650 mg to about 1200 mg to the patient every two months. 
     
     
         27 . The method according to  claim 26 , wherein the administration of the injectable preparation results in the total amount of aripiprazole of about 960 mg to the patient every two months. 
     
     
         28 . The method according to  claim 25 , wherein the about once every two months comprises about once every 42 days to 70 days. 
     
     
         29 . The method according to  claim 28 , wherein the once every two months comprises once every 54 days to 58 days. 
     
     
         30 . The method according to  claim 25 , wherein the patient has schizophrenia. 
     
     
         31 . The method according to  claim 25 , wherein the patient has bipolar I disorder. 
     
     
         32 . The method according to  claim 25 , wherein administering intramuscularly to the patient is at a gluteal muscle. 
     
     
         33 . The method according to  claim 25 , wherein the injectable preparation further comprises: water, and a suspending agent comprising polyvinylpyrrolidone, polyethylene glycol, and carboxymethylcellulose or a salt thereof, wherein aripiprazole or a salt thereof has a mean primary particle diameter ranging from about 0.5 μm to about 30 μm and the concentration of aripiprazole or a salt thereof ranges from about 200 mg/m L to about 600 mg/m L. 
     
     
         34 . The method according to  claim 25 , wherein the injectable preparation further comprises: water for injection, and a suspending agent comprising polyvinylpyrrolidone, polyethylene glycol, and carboxymethylcellulose or a salt thereof, wherein the aripiprazole or a salt thereof is aripiprazole monohydrate, the aripiprazole monohydrate has a mean primary particle diameter ranging from about 2 μm to about 5 μm, and the concentration of aripiprazole in the injectable preparation is about 300 mg/mL which is calculated based on the anhydrous form of aripiprazole. 
     
     
         35 . The method according to  claim 25 , wherein an area under the concentration-time curve (AUC) of aripiprazole from time zero to 56 days postdose following a plurality of administration of the injectable preparation is substantially equal to a twofold AUC of aripiprazole from time zero to 28 days postdose following a plurality of administration of an aripiprazole intramuscular (IM) depot formulation. 
     
     
         36 . The method according to  claim 25 , further comprising administering orally to the patient a solid dosage form comprising aripiprazole or a salt thereof, wherein the injectable preparation and the solid dosage form are administered to the patient on a first day, and the solid dosage form is administered for consecutive 5 to 15 days from the first day. 
     
     
         37 . A method of treating a patient with schizophrenia or bipolar I disorder comprising:
 administering to the patient at a gluteal muscle an injectable preparation comprising aripiprazole or a salt thereof,   wherein the patient is administered the injectable preparation about once every 56 days, and the amount of aripiprazole in the injectable preparation is about 960 mg.   
     
     
         38 . The method according to  claim 37 , wherein the injectable preparation further comprises: water, and a suspending agent comprising polyvinylpyrrolidone, polyethylene glycol, and carboxymethylcellulose or a salt thereof, wherein aripiprazole or a salt thereof has a mean primary particle diameter ranging from about 0.5 μm to about 30 μm, and the concentration of aripiprazole in the injectable preparation is about 300 mg/mL. 
     
     
         39 . The method according to  claim 37 , wherein the injectable preparation further comprises: water for injection, and a suspending agent comprising polyvinylpyrrolidone, polyethylene glycol, and carboxymethylcellulose or a salt thereof, wherein the aripiprazole or a salt thereof is aripiprazole monohydrate, the aripiprazole monohydrate has a mean primary particle diameter ranging from about 2 μm to about 5 μm, and the concentration of aripiprazole in the injectable preparation is about 300 mg/mL which is calculated based on the anhydrous form of aripiprazole. 
     
     
         40 . The method according to  claim 37 , wherein an area under the concentration-time curve (AUC) of aripiprazole from time zero to 56 days postdose following a plurality of administration of the injectable preparation is substantially equal to a twofold AUC of aripiprazole from time zero to 28 days postdose following a plurality of administration of an aripiprazole intramuscular (IM) depot formulation. 
     
     
         41 . The method of according to  claim 37 , further comprising administering aripiprazole in a solid dosage form orally, and the solid dosage form is administered in an amount in a range of 10 mg to 20 mg per day for consecutive 5 to 15 days with the first administration of the injectable preparation. 
     
     
         42 . The method according to  claim 37 , further comprising administering 10 mg to 20 mg of aripiprazole in a solid dosage form orally per day for consecutive 7 days with the first administration of the injectable preparation. 
     
     
         43 . A method of administering an injectable preparation comprising aripiprazole or a salt thereof to a patient with schizophrenia or bipolar I disorder comprising:
 administering orally to the patient 10 to 20 mg/day of aripiprazole or a salt thereof for consecutive 5 to 15 days from a first day;   administering intramuscularly to the patient the injectable preparation once every about 56 days (every about 8 weeks or two months),   wherein the injectable preparation comprising about 650 mg to 1200 mg of aripiprazole is administered on the first day, and a series of the administrations allows the mean plasma level of aripiprazole to maintain 90 ng/mL or more.   
     
     
         44 . The method according to  claim 43 , wherein the method does not comprise a further oral administration of aripiprazole or a salt thereof. 
     
     
         45 . A method of administering a prefilled sol-gel formed injectable preparation comprising aripiprazole or a salt thereof to a patient in need thereof, comprising:
 administering 50 to 300 mg of aripiprazole, as a total amount, orally and simultaneously or consecutively from a first day to the 15th day or less; and   administering the prefilled sol-gel formed injectable preparation comprising 650 to 1200 mg of aripiprazole at a gluteal muscle on the first day; followed by   administering the prefilled sol-gel formed injectable preparation comprising about 650 mg to 1200 mg of aripiprazole at a gluteal muscle once every about 56 days,   wherein a series of the administrations allows the mean plasma level of aripiprazole to maintain 90 ng/mL or more.   
     
     
         46 . The method according to  claim 45 , wherein the prefilled sol-gel formed injectable preparation is an injectable preparation comprising 300 mg/mL of aripiprazole, having a thixotropic property. 
     
     
         47 . The method according to  claim 45 , wherein the injectable preparation further comprises a suspending agent selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, carboxymethylcellulose or a salt thereof, and any combination thereof, and the aripiprazole or a salt thereof is aripiprazole monohydrate. 
     
     
         48 . A method of administering a long acting injectable preparation comprising aripiprazole or a salt thereof to a patient in need thereof, comprising:
 administering to the patient the injectable preparation comprising 650 to 1200 mg of aripiprazole at a gluteal muscle once every about 56 days,   wherein the patient has a stable plasma level of aripiprazole by being subject to administration of aripiprazole but is in need of additional administration of aripiprazole, the injectable preparation is in a dosage form of a prefilled sol-gel formed injection, and a series of the administrations allows the mean plasma level of aripiprazole to maintain 90 ng/mL or more.