Methods for the administration of iloperidone

Abstract

The present invention relates to methods for the identification of genetic polymorphisms that may be associated with a risk for QT prolongation after treatment with iloperidone and related methods of administering iloperidone to patients with such polymorphisms.

What is claimed is: 
     
         1 . A method for treating a patient with an active pharmaceutical ingredient that is iloperidone, a pharmaceutically acceptable salt of iloperidone, an active metabolite of iloperidone that is P88 or P95, or a pharmaceutically acceptable salt of P88 or P95, comprising the steps of:
 determining the patient's CYP2D6 genotype; and   administering to the patient an effective amount of the active pharmaceutical ingredient, whereby the amount of the active pharmaceutical ingredient is determined based on the patient's CYP2D6 genotype.   
     
     
         2 . The method of  claim 1 , wherein the amount of the active pharmaceutical ingredient is decreased if the genotype indicates decreased enzymatic activity of the CYP2D6 enzyme relative to the wild type. 
     
     
         3 . The method of  claim 1 , wherein the amount of the active pharmaceutical ingredient is decreased if the patient's CYP2D6G1846A genotype is AA. 
     
     
         4 . The method of  claim 1 , wherein the amount of the active pharmaceutical ingredient is decreased if the patient's CYP2D6G1846A genotype is GA. 
     
     
         5 . The method of  claim 1 , wherein the amount of the active pharmaceutical ingredient is decreased if the patient's CYP2D6C100T genotype is TT. 
     
     
         6 . The method of  claim 1 , wherein the amount of the active pharmaceutical ingredient is decreased if the patient's CYP2D6C100T genotype is CT. 
     
     
         7 . The method of  claim 1 , wherein the patient is suffering from at least one of schizophrenia, schizoaffective disorder, depression, bipolar mania/depression, cardiac arrhythmia, Tourette's Syndrome, a psychotic disorder, a delusional disorder, and schizophreniform disorder. 
     
     
         8 . The method of  claim 7 , wherein the patient is at risk for a prolonged QT interval. 
     
     
         9 . A method for treating a patient who is a CYP2D6 poor metabolizer with a pharmaceutically active ingredient that is iloperidone, a pharmaceutically acceptable salt of iloperidone, an active metabolite of iloperidone that is P88 or P95, or a pharmaceutically acceptable salt of P88 or P95, wherein the patient is administered a lower dosage than would be given to an individual who is not a CYP2D6 poor metabolizer. 
     
     
         10 . The method of  claim 9 , wherein the patient is determined to be a CYP2D6 poor metabolizer based on at least one of the patient's genotype, the patient's phenotype, and the fact that the patient is being treated with an agent that reduces CYP2D6 activity. 
     
     
         11 . The method of  claim 9 , wherein the patient's genotype includes at least one CYP2D6 allele selected from a group consisting of 2549 A deletion, 1846 G>A, 1707 T deletion, 2935 A>C, 1758 G>T, 2613−2615 AGA deletion, 1023 C>T, 2850 C>T, 4180G>C, 1659 G>A, 1661 G>C, 2850 C>T, 3183 G>A, −1584 C, −1235 A>G, −740C>T, and −678 G>A. 
     
     
         12 . The method of  claim 10 , wherein the patient's genotype includes at least one deletion of the CYP2D6 gene. 
     
     
         13 . The method of  claim 11 , wherein the patient's genotype includes a CYP2D7 gene conversion in intron 1. 
     
     
         14 . The method of  claim 9 , wherein the patient is suffering from at least one of schizophrenia, schizoaffective disorder, depression, bipolar mania/depression, cardiac arrhythmia, Tourette's Syndrome, a psychotic disorder, a delusional disorder, and schizophreniform disorder. 
     
     
         15 . A method of treating a patient with a pharmaceutically active ingredient that is iloperidone, a pharmaceutically acceptable salt of iloperidone, an active metabolite of iloperidone that is P88 or P95, or a pharmaceutically acceptable salt of P88 or P95 comprising the steps of:
 determining whether the patient is being administered a CYP2D6 inhibitor; and   reducing the dosage of drug if the patient is being administered a CYP2D6 inhibitor.   
     
     
         16 . The method of  claim 15 , wherein the CYP2D6 inhibitor includes at least one of paroxetine, dolasetron, venlafaxin, and fluoxetine. 
     
     
         17 . The method of  claim 15 , wherein the patient is suffering from at least one of schizophrenia, schizoaffective disorder, depression, bipolar mania/depression, cardiac arrhythmia, Tourette's Syndrome, a psychotic disorder, a delusional disorder, and schizophreniform disorder.