ARIPIPRAZOLE LAUROXIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C36H51Cl2N3O4
Molecular Weight	660.714
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCCCCCCCC(=O)OCN1C(=O)CCC2=C1C=C(OCCCCN3CCN(CC3)C4=CC=CC(Cl)=C4Cl)C=C2

InChI

InChIKey=DDINXHAORAAYAD-UHFFFAOYSA-N

InChI=1S/C36H51Cl2N3O4/c1-2-3-4-5-6-7-8-9-10-16-35(43)45-28-41-33-27-30(19-17-29(33)18-20-34(41)42)44-26-12-11-21-39-22-24-40(25-23-39)32-15-13-14-31(37)36(32)38/h13-15,17,19,27H,2-12,16,18,20-26,28H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12784105/, https://www.ncbi.nlm.nih.gov/pubmed/12587943, https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0000157/

Aripiprazole is the first next-generation atypical antipsychotic. The unique actions of aripiprazole in humans are likely a combination of "functionally selective" activation of D(2) (and possibly D(3))-dopamine receptors and serotonin 5-HT(1A) receptors, coupled with inhibition of 5-HT(2A) receptors. Aripiprazole was approved by FDA (Abilify trade name) for the treatment of schizophrenia; manic and mixed episodes associated with bipolar I disorder; major depressive disorder; irritability associated with autistic disorder; Tourette’s disorder and agitation associated with schizophrenia or bipolar mania.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Partial Agonist 290	0.34 nM [Ki]
Serotonin 2a (5-HT2a) receptor 231 Target ID: CHEMBL224 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Antagonist 2778	8.7 nM [Ki]
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Partial Agonist 290	5.6 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 298 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Primary	Approved 8429	ABILIFY Approved Use ABILIFY is an atypical antipsychotic. The oral formulations are indicated for: Schizophrenia, Acute Treatment of Manic and Mixed Episodes associated with Bipolar I, Adjunctive Treatment of Major Depressive Disorder, Irritability Associated with Autistic Disorder, Treatment of Tourette’s disorder, The injection is indicated for: Agitation associated with schizophrenia or bipolar mania Launch Date 1.03731842E12
Bipolar I disorder 17 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Primary	Approved 8429	ABILIFY Approved Use ABILIFY is an atypical antipsychotic. The oral formulations are indicated for: Schizophrenia, Acute Treatment of Manic and Mixed Episodes associated with Bipolar I, Adjunctive Treatment of Major Depressive Disorder, Irritability Associated with Autistic Disorder, Treatment of Tourette’s disorder, The injection is indicated for: Agitation associated with schizophrenia or bipolar mania Launch Date 1.03731842E12
Major depressive disorder 173 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Primary	Approved 8429	ABILIFY Approved Use ABILIFY is an atypical antipsychotic. The oral formulations are indicated for: Schizophrenia, Acute Treatment of Manic and Mixed Episodes associated with Bipolar I, Adjunctive Treatment of Major Depressive Disorder, Irritability Associated with Autistic Disorder, Treatment of Tourette’s disorder, The injection is indicated for: Agitation associated with schizophrenia or bipolar mania Launch Date 1.03731842E12
Autism 19 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Primary	Approved 8429	ABILIFY Approved Use ABILIFY is an atypical antipsychotic. The oral formulations are indicated for: Schizophrenia, Acute Treatment of Manic and Mixed Episodes associated with Bipolar I, Adjunctive Treatment of Major Depressive Disorder, Irritability Associated with Autistic Disorder, Treatment of Tourette’s disorder, The injection is indicated for: Agitation associated with schizophrenia or bipolar mania Launch Date 1.03731842E12
Tourette's syndrome 20 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Primary	Approved 8429	ABILIFY Approved Use ABILIFY is an atypical antipsychotic. The oral formulations are indicated for: Schizophrenia, Acute Treatment of Manic and Mixed Episodes associated with Bipolar I, Adjunctive Treatment of Major Depressive Disorder, Irritability Associated with Autistic Disorder, Treatment of Tourette’s disorder, The injection is indicated for: Agitation associated with schizophrenia or bipolar mania Launch Date 1.03731842E12
Agitation associated with schizophrenia or bipolar mania 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf	Primary	Approved 8429	ABILIFY Approved Use ABILIFY is an atypical antipsychotic indicated as oral formulations for the: Treatment of schizophrenia (1.1) Adults: Efficacy was established in four 4-6 week trials and one maintenance trial in patients with schizophrenia (14.1) Adolescents (ages 13-17): Efficacy was established in one 6-week trial in patients with schizophrenia (14.1) Acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy and as an adjunct to lithium or valproate (1.2) Adults: Efficacy was established in four 3-week monotherapy trials and one 6-week adjunctive trial in patients with manic or mixed episodes (14.2) Pediatric Patients (ages 10-17): Efficacy was established in one 4-week monotherapy trial in patients with manic or mixed episodes (14.2) Maintenance treatment of bipolar I disorder, both as monotherapy and as an adjunct to lithium or valproate (1.2) Adults: Efficacy was established in one maintenance monotherapy trial and in one maintenance adjunctive trial (14.2) Adjunctive treatment of major depressive disorder (MDD) (1.3) Adults: Efficacy was established in two 6-week trials in patients with MDD who had an inadequate response to antidepressant therapy during the current episode (14.3) Treatment of irritability associated with autistic disorder (1.4) Pediatric Patients (ages 6-17 years): Efficacy was established in two 8-week trials in patients with autistic disorder (14.4) as an injection for the: Acute treatment of agitation associated with schizophrenia or bipolar I disorder (1.5) Adults: Efficacy was established in three 24-hour trials in agitated patients with schizophrenia or manic/mixed episodes of bipolar I disorder (14.5) 1.1 Schizophrenia ABILIFY is indicated for the treatment of schizophrenia. The efficacy of ABILIFY was established in four 4-6 week trials in adults and one 6-week trial in adolescents (13 to 17 years). Maintenance efficacy was demonstrated in one trial in adults and can be extrapolated to adolescents [see CLINICAL STUDIES (14.1) Launch Date 1.03731842E12

C_max

Value	Dose	Co-administered	Analyte	Population
163 ng/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/15257633	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ARIPIPRAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
2947 ng × h/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/15257633	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ARIPIPRAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
52.9 h REVIEW https://www.ncbi.nlm.nih.gov/pubmed/15257633	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ARIPIPRAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% REVIEW https://www.ncbi.nlm.nih.gov/pubmed/15257633	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ARIPIPRAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg 1 times / day multiple, oral Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: multiple Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18626272	unhealthy, 10-17 years n = 6 Health Status: unhealthy Condition: Psychiatric Disorders Age Group: 10-17 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/18626272	Other AEs: Abdominal pain upper, Vomiting... Other AEs: Abdominal pain upper (17%) Vomiting (17%) Dizziness (17%) Headache (50%) Sedation (33%) Somnolence (17%) Sources: https://pubmed.ncbi.nlm.nih.gov/18626272
2 mg single, intravenous Dose: 2 mg Route: intravenous Route: single Dose: 2 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18563956/	healthy, 35 years (range: 18-45 years) n = 16 Health Status: healthy Age Group: 35 years (range: 18-45 years) Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/18563956/	Sources: https://pubmed.ncbi.nlm.nih.gov/18563956/
45 mg single, intramuscular Highest studied dose Dose: 45 mg Route: intramuscular Route: single Dose: 45 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18563956/	unhealthy, 39 years (range: 18-65 years) n = 4 Health Status: unhealthy Condition: schizophrenia Age Group: 39 years (range: 18-65 years) Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/18563956/	Sources: https://pubmed.ncbi.nlm.nih.gov/18563956/
195 mg single, oral Overdose Dose: 195 mg Route: oral Route: single Dose: 195 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf	unhealthy, < 12 years n = 10 Health Status: unhealthy Age Group: < 12 years Population Size: 10 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf	Other AEs: Vomiting, Somnolence... Other AEs: Vomiting Somnolence Tremor Acidosis Aggression Aspartate aminotransferase increased Atrial fibrillation Coma Confusional state Convulsion Blood creatine phosphokinase increased Depressed level of consciousness Hypertension Hypokalemia Hypotension Lethargy Loss of consciousness QT prolonged Aspiration pneumonia Respiratory arrest Status epilepticus Tachycardia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00102063	unhealthy, adolescent n = 100 Health Status: unhealthy Condition: schizophrenia Age Group: adolescent Population Size: 100 Sources: https://clinicaltrials.gov/ct2/show/NCT00102063	Other AEs: Extrapyramidal disorder, Neuroleptic malignant syndrome... Other AEs: Extrapyramidal disorder (serious, 1 patient) Neuroleptic malignant syndrome (serious, 1 patient) Aggression (serious, 1 patient) Schizophrenia (serious, 1 patient) Nausea (below serious, 9 patients) Nasopharyngitis (below serious, 5 patients) Dizziness (below serious, 7 patients) Extrapyramidal disorder (below serious, 13 patients) Headache (below serious, 16 patients) Somnolence (below serious, 11 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00102063
30 mg 1 times / day steady, oral Dose: 30 mg, 1 times / day Route: oral Route: steady Dose: 30 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00102063	unhealthy, adolescent n = 102 Health Status: unhealthy Condition: schizophrenia Age Group: adolescent Population Size: 102 Sources: https://clinicaltrials.gov/ct2/show/NCT00102063	Other AEs: Varicella, Depression... Other AEs: Varicella (serious, 1 patient) Depression (serious, 1 patient) Schizophrenia (serious, 1 patient) Suicidal ideation (serious, 1 patient) Thrombophlebitis (serious, 1 patient) Nausea (below serious, 10 patients) Nasopharyngitis (below serious, 5 patients) Dizziness (below serious, 4 patients) Extrapyramidal disorder (below serious, 22 patients) Headache (below serious, 11 patient) Somnolence (below serious, 22 patients) Tremor (below serious, 12 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00102063
1080 mg single, oral Overdose Dose: 1080 mg Route: oral Route: single Dose: 1080 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf	Other AEs: Vomiting, Somnolence... Other AEs: Vomiting Somnolence Tremor Acidosis Aggression Aspartate aminotransferase increased Atrial fibrillation Coma Confusional state Convulsion Blood creatine phosphokinase increased Depressed level of consciousness Hypertension Hypokalemia Hypotension Lethargy Loss of consciousness QT prolonged Aspiration pneumonia Respiratory arrest Status epilepticus Tachycardia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: Dementia-Related Psychosis Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf	Other AEs: Adverse event... Other AEs: Adverse event (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021729lbl.pdf
15 mg 1 times / day steady, oral (max) Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00198107	unhealthy, children n = 40 Health Status: unhealthy Condition: autism Age Group: children Population Size: 40 Sources: https://clinicaltrials.gov/ct2/show/NCT00198107	Other AEs: Constipation, Diarrhea... Other AEs: Constipation (below serious, 8 patients) Diarrhea (below serious, 7 patients) Nausea (below serious, 2 patients) Abdominal discomfort (below serious, 7 patients) Vomiting (below serious, 15 patients) Decreased appetite (below serious, 12 patients) Increased appetite (below serious, 16 patients) Drowsiness (below serious, 5 patients) Tiredness (below serious, 21 patient) Fever (below serious, 3 patients) Weight gain (below serious, 8 patients) Muscle rigidity (below serious, 3 patients) Tremor (below serious, 3 patients) Nervousness (below serious, 3 patients) Repetitive speech (below serious, 3 patients) Restlessness (below serious, 3 patients) Feeling sad (below serious, 3 patients) Self injurious behavior (below serious, 3 patients) Enuresis (below serious, 3 patients) Dizziness (below serious, 4 patients) Nose bleed (below serious, 3 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00198107
15 mg 1 times / day steady, oral Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01338298	unhealthy n = 20 Health Status: unhealthy Condition: schizophrenia Sex: F Population Size: 20 Sources: https://clinicaltrials.gov/ct2/show/NCT01338298	Other AEs: Abdominal pain, Bruising... Other AEs: Abdominal pain (below serious, 7 patients) Bruising (below serious, 2 patients) Constipation (below serious, 6 patients) Diarrhea (below serious, 9 patients) Dizziness (below serious, 5 patients) Dry mouth (below serious, 6 patients) Enuresis (below serious, 5 patients) Headache (below serious, 6 patients) Insomnia (below serious, 8 patients) Malaise (below serious, 7 patients) Mucosal ulceration (below serious, 4 patients) Nausea (below serious, 10 patients) Restlessness (below serious, 5 patients) Sedation (below serious, 7 patients) Tinnitus (below serious, 7 patients) Tremor (below serious, 8 patients) Vomiting (below serious, 10 patients) Weight loss (below serious, 4 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01338298
20 mg 1 times / day steady, oral (max) Dose: 20 mg, 1 times / day Route: oral Route: steady Dose: 20 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00489866	unhealthy n = 7 Health Status: unhealthy Condition: posttraumatic stress disorder Population Size: 7 Sources: https://clinicaltrials.gov/ct2/show/NCT00489866	Other AEs: Restlessness, Decreased activity... Other AEs: Restlessness (below serious, 2 patients) Decreased activity (below serious, 1 patient) Drowsiness (below serious, 2 patients) Vertigo (below serious, 1 patient) Cold extremities (below serious, 1 patient) Blurred vision (below serious, 2 patients) Sexual disorder NOS (below serious, 2 patients) Joint stiffness (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00489866
20 mg 1 times / day steady, oral Dose: 20 mg, 1 times / day Route: oral Route: steady Dose: 20 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00497055	unhealthy n = 45 Health Status: unhealthy Condition: Methamphetamine Dependence Population Size: 45 Sources: https://clinicaltrials.gov/ct2/show/NCT00497055	Other AEs: Rhabdomyolysis, Pneumonia... Other AEs: Rhabdomyolysis (serious, 1 patient) Pneumonia (serious, 1 patient) Cellulitis (serious, 1 patient) Abrasions (below serious, 3 patients) Akathisia (below serious, 12 patients) Drowsiness (below serious, 6 patients) Fatigue (below serious, 8 patients) Depressed mood (below serious, 3 patients) Hypernatremia (below serious, 4 patients) Hypocalcemia (below serious, 3 patients) ALT increased (below serious, 8 patients) Aspartate aminotransferase increased (below serious, 6 patients) Restlessness (below serious, 4 patients) Sleep disturbance (below serious, 3 patients) Infection upper respiratory (below serious, 6 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00497055
400 mg 1 times / 4 weeks steady, oral Dose: 400 mg, 1 times / 4 weeks Route: oral Route: steady Dose: 400 mg, 1 times / 4 weeks Sources: https://clinicaltrials.gov/ct2/show/NCT00705783	unhealthy n = 269 Health Status: unhealthy Condition: schizophrenia Population Size: 269 Sources: https://clinicaltrials.gov/ct2/show/NCT00705783	Other AEs: Suicidal ideation, Gun shot wound... Other AEs: Suicidal ideation (serious, 2 patients) Gun shot wound (serious, 1 patient) Injury (serious, 1 patient) Multiple injuries (serious, 1 patient) Diabetes mellitus (serious, 1 patient) Hyperglycaemia (serious, 1 patient) Pancreatic carcinoma (serious, 1 patient) Hallucination, auditory (serious, 1 patient) Suicide attempt (serious, 1 patient) Headache (below serious, 16 patients) Insomnia (below serious, 27 patients) Tremor (below serious, 16 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00705783

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 P-gp 1461 BCRP 699	CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667 UGT 192 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0	not significant	unlikely (co-administration study) Comment: aripiprazole had no effect ont the PK of omeprazole Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0	not significant	unlikely (co-administration study) Comment: aripiprazole had no effect on the PK of warfarin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0	not significant	unlikely (co-administration study) Comment: aripiprazole had no effect on the PK of of dextromethorphan Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0	not significant	unlikely (co-administration study) Comment: aripiprazole had no effect on the PK of of dextromethorphan Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0	not significant	unlikely Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-436_Abilify_biopharmr_P1.pdf#page=43 Page: 43.0
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22847220/	yes [IC50 1.2 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22847220/	yes [IC50 3.5 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf#page=5 Page: 5.0	no
P-gp 1537	substrate 3367 Sources: https://www.futuremedicine.com/doi/abs/10.2217/pgs.11.55 Page: 1.0	yes
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf#page=29 Page: 29.0	yes	yes (co-administration study) Comment: Coadministration of aripiprazole with quinidine, a potent inhibitor of CYP2D6, increased the AUC of aripiprazole by 112% but decreased the AUC of its active metabolite, dehydroaripiprazole, by 35%; PHARMACOGENOMIC STUDY: 82% increase in aripiprazole systemic exposure in CYP2D6 PM compared to EM, net increase of aripiprazole exposure is greater than 60%, total body clearance of aripiprazole in PM decreased by 40%, not adequately studied in PM patients; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf#page=29 Page: 29.0
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf#page=29 Page: 29.0	yes	yes (co-administration study) Comment: Coadministration of ketoconazole increased the AUC of aripiprazole and its active metabolite by 63% and 77%, respectively; Coadministration of carbamazepine, a potent CYP3A4 inducer, resulted in an approximate 70% decrease in Cmax and AUC values of both aripiprazole and its active metabolite, dehydro-aripiprazole; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf#page=29 Page: 29.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472675/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31236	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31236
ChemicalBook	CB42487193	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB42487193
ChemicalBook	CB8210870	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8210870
MolPort	MolPort-002-885-808	https://www.molport.com/shop/molecule-link/MolPort-002-885-808
MolPort	MolPort-046-939-776	https://www.molport.com/shop/molecule-link/MolPort-046-939-776
Selleck Chemicals	aripiprazole-abilify	http://www.selleckchem.com/products/aripiprazole-abilify.html
ZINC	ZINC000001851149	http://zinc15.docking.org/substances/ZINC000001851149
eMolecules	901410	https://www.emolecules.com/cgi-bin/more?vid=901410

PubMed

Title	Date	PubMed
The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice.	2003	14728084
Similarities and differences among antipsychotics.	2003	14680420
Choice of maintenance medication for schizophrenia.	2003	14680416
Aripiprazole-induced improvement in tardive dyskinesia.	2003 Dec	14733461
Medication developments in the treatment of mental illness.	2003 Dec	14696289
Relationship of atypical antipsychotics with development of diabetes mellitus.	2003 Dec	14632602
Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia.	2003 Dec	14609439
Aripiprazole.	2003 Dec 1	14686220
Aripiprazole and extrapyramidal symptoms.	2003 Nov	14566162
Serotonin receptors: their key role in drugs to treat schizophrenia.	2003 Oct	14642974
Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo-controlled 26-week study.	2003 Sep	14628980
Aripiprazole for schizophrenia.	2004	15106256
Aripiprazole: in acute mania associated with bipolar I disorder.	2004	15089107
Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications.	2004	15025545
Dopamine partial agonists: a new class of antipsychotic.	2004	15015905
Focus on aripiprazole.	2004	15006016
Using antipsychotic agents in older patients.	2004	14994733
Weight gain associated with atypical antipsychotic use in children and adolescents: prevalence, clinical relevance, and management.	2004	14969568
Dose response and dose equivalence of antipsychotics.	2004 Apr	15206667
Gateways to clinical trials.	2004 Apr	15148527
The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update.	2004 Apr	15119912
Excessive somnolence from aripiprazole in a child.	2004 Apr	15098808
Drug induced weight gain, an impediment to successful pharmacotherapy: focus on antipsychotics.	2004 Apr	15058313
Aripiprazole (OPC-14597) fully substitutes for the 5-HT1A receptor agonist LY293284 in the drug discrimination assay in rats.	2004 Apr	14647959
The novel antipsychotic aripiprazole is a partial agonist at short and long isoforms of D2 receptors linked to the regulation of adenylyl cyclase activity and prolactin release.	2004 Apr 2	15019558
Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns.	2004 Apr 27	15109398
Aripirazole-olanzapine combination for treatment of schizophrenia.	2004 Feb	15065751
Aripiprazole, a novel atypical antipsychotic drug.	2004 Feb	14998222
Naturalistic studies of second generation antipsychotics in the treatment of schizophrenia.	2004 Feb	14965235
A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation.	2004 Feb	14965234
Pharmacogenomic-guided rational therapeutic drug monitoring: conceptual framework and application platforms for atypical antipsychotics.	2004 Feb	14965233
Atypical antipsychotics: pharmacokinetics, therapeutic drug monitoring and pharmacological interactions.	2004 Feb	14965232
Schizophrenia: from dopamine to glutamate and back.	2004 Feb	14965231
Aripiprazole is effective against the symptoms of schizophrenia and schizoaffective disorder.	2004 Feb	14769657
Aripiprazole and Parkinson's disease psychosis.	2004 Feb	14754792
Pharmacokinetics, tolerability, and safety of aripiprazole following multiple oral dosing in normal healthy volunteers.	2004 Feb	14747427
Selection of atypical antipsychotics for the management of schizophrenia.	2004 Feb	14742771
Aripiprazole possibly worsens psychosis.	2004 Jan	15101571
Worsened agitation with aripiprazole: adverse effect of dopamine partial agonism?	2004 Jan	14976671
In vivo effects of aripiprazole on cortical and striatal dopaminergic and serotonergic function.	2004 Jan 1	14709325
Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience.	2004 Jan-Feb	15090928
Gateways to clinical trials.	2004 Jan-Feb	14988742
The case for atypical antipsychotics in bipolar disorder.	2004 Jan-Mar	15147051
Clinical utilization of atypical antipsychotics in pregnancy and lactation.	2004 Jul-Aug	15150376
Evidence-based pharmacotherapy of schizophrenia.	2004 Jun	15043765
Aripiprazole, a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain.	2004 Jun 16	15189766
Gateways to clinical trials.	2004 Mar	15071612
International Congress of Biological Psychiatry. 8-13 February 2004, Sydney, Australia.	2004 Mar	15017455
Aripiprazole: a comprehensive review of its pharmacology, clinical efficacy, and tolerability.	2004 May	15220010
Aripiprazole is effective for relapse prevention in people with chronic stable schizophrenia.	2004 May	15107337

Patents

Sample Use Guides

In Vivo Use Guide

In adults with schizophrenia the recommended starting and target dose for aripiprazole (ABILIFY) is 10 or 15 mg/day. In adolescents the target dose is 10 mg/day. In adults with Bipolar I Disorder, the recommended starting dose is 15 mg given once daily as monotherapy and 10 mg to 15 mg given once daily as adjunctive therapy with lithium or valproate. In pediatric patients (10 to 17 years) with Bipolar I Disorder, the starting dose as monotherapy is 2 mg/day, with titration to 5 mg/day after 2 days, and a target dose of 10 mg/day after 2 additional days. In adults with Major Depressive Disorder, the recommended starting dose as adjunctive treatment for patients already taking an antidepressant is 2 to 5 mg/day. The recommended dosage range is 2 to 15 mg/day. In pediatric patients with Irritability Associated with Autistic Disorder, dosing should be initiated at 2 mg/day. The dose should be increased to 5 mg/day, with subsequent increases to 10 or 15 mg/day if needed. In pediatric patient with Tourette’s Disorder, the recommended dosage is 5 to 20 mg/day. In adults with Agitation Associated with Schizophrenia or Bipolar Mania, the recommended dose is 9.75 mg. The recommended dosage range is 5.25 to 15 mg.

Route of Administration: Other

In Vitro Use Guide

PC12 cells were treated with 0.001-1.0 uM aripiprazole in the presence of NGF (2.5ng/ml). Aripiprazole significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration-dependent manner.

Name

Type

Language

ARIPIPRAZOLE LAUROXIL

Official Name

English

RDC-3317

Code

English

ALKS 9072

Code

English

ARISTADA INITIO

Brand Name

English

ARISTADA

Brand Name

English

ARIPIPRAZOLE LAUROXIL [ORANGE BOOK]

Common Name

English

ARIPIPRAZOLE LAUROXIL [USAN]

Common Name

English

ALKS-9072

Code

English

RDC3317

Code

English

DODECANOIC ACID, (7-(4-(4-(2,3-DICHLOROPHENYL)-1-PIPERAZINYL)BUTOXY)-3,4-DIHYDRO-2-OXO-1(2H)-QUINOLINYL)METHYL ESTER

Common Name

English

ARIPIPRAZOLE LAUROXIL [MI]

Common Name

English

(7-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl dodecanoate

Systematic Name

English

Aripiprazole lauroxil [WHO-DD]

Common Name

English

ALKS-9070

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C29710