Chemical: Drug
aripiprazole

last updated 02/07/2014

1. DPWG Guideline for aripiprazole and CYP2D6

Summary

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group (DPWG) recommends reducing maximum dose of aripiprazole for patients carrying poor metabolizer alleles of CYP2D6.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group (DPWG) has evaluated therapeutic dose recommendations for aripiprazole based on CYP2D6 genotypes [Article:21412232]. They recommend reducing maximum dose of aripiprazole for patients carrying poor metabolizer alleles of CYP2D6.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (two inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) alleles)Reduce maximum dose to 10 mg/day (67% of the maximum recommended daily dose).Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); INR 4.5-6.0; neutropenia 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l.
IM (two decreased-activity (*9, *10, *17, *29, *36, *41) alleles or carrying one active (*1, *2, *33, *35) and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele, or carrying one decreased-activity (*9, *10, *17, *29, *36, *41) allele and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele)No recommendations.Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Minor clinical effect (S): QTc prolongation (<450 ms female, <470 ms male); INR increase < 4.5; Kinetic effect (S)
UM (a gene duplication in absence of inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) or decreased-activity (*9, *10, *17, *29, *36, *41) alleles)No recommendations.----
  • *See Methods or PMID: 18253145 for definition of "good quality."
  • S: statistically significant difference.
  • Please see attached PDF for detailed information about the evaluated studies: Aripiprazole CYP2D6 (^aripiprazole_CYP2D6_271111.pdf|link tip)


Annotated Labels

  1. FDA Label for aripiprazole and CYP2D6
  2. EMA Label for aripiprazole and CYP2D6,CYP3A4
  3. HCSC Label for aripiprazole and CYP2D6

last updated 06/13/2016

1. FDA Label for aripiprazole and CYP2D6

Actionable PGx

Summary

Elimination of aripiprazole is mainly via metabolism by CYP2D6 and CYP3A4 - the FDA-approved drug label contains information regarding dose adjustment in patients who are CYP2D6 poor metabolizers, or in patients taking concomittant drugs that may inhibit or induce CYP2D6 or CYP3A4.

There's more of this label. Read more.


last updated 10/25/2013

2. EMA Label for aripiprazole and CYP2D6,CYP3A4

Actionable PGx

Summary

The EMA European Public Assessment Report (EPAR) recommends dose adjustments when aripiprazole is taken with CYP3A4 inhibitors in CYP2D6 poor metabolizers, or concomitant use of CYP3A4 or CYP2D6 inhibitors, or CYP3A4 inducers.

There's more of this label. Read more.


last updated 06/08/2015

3. HCSC Label for aripiprazole and CYP2D6

Actionable PGx

Summary

The product monograph for aripiprazole (ABILIFY) notes that CYP2D6 poor metabolizers have approximately an 80% increase in aripiprazole exposure and approximately a 30% decrease in exposure to the active metabolite compared to CYP2D6 extensive metabolizers.

There's more of this label. Read more.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for aripiprazole

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA CYP2D6 *1 N/A N/A N/A
No VIP available CA VA CYP2D6 *2 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *3 N/A N/A N/A
No VIP available CA VA CYP2D6 *4 N/A N/A N/A
No VIP available CA VA CYP2D6 *5 N/A N/A N/A
No VIP available CA VA CYP2D6 *6 N/A N/A N/A
No VIP available CA VA CYP2D6 *10 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *21 N/A N/A N/A
No VIP available CA VA CYP2D6 *41 N/A N/A N/A
No VIP available No Clinical Annotations available VA
CYP2D6 poor metabolizer N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs1011313 NC_000006.11:g.15633432T>C, NC_000006.12:g.15633201T>C, NG_009309.1:g.34840A>G, NM_001271667.1:c.-22+4543A>G, NM_001271668.1:c.171+4543A>G, NM_001271669.1:c.117+4543A>G, NM_032122.4:c.222+4543A>G, NM_183040.2:c.222+4543A>G, NR_036448.1:n.550+4543A>G, XM_005249447.1:c.183+4543A>G, XM_005249447.3:c.183+4543A>G, XM_011514936.1:c.132+4543A>G, rs60265531, rs74291082
T > C
SNP
No VIP available CA VA
rs1049353 NC_000006.11:g.88853635C>T, NC_000006.12:g.88143916C>T, NM_001160226.1:c.1359G>A, NM_001160258.1:c.1359G>A, NM_001160259.1:c.1359G>A, NM_016083.4:c.1359G>A, NM_033181.3:c.1260G>A, NP_001153698.1:p.Thr453=, NP_001153730.1:p.Thr453=, NP_001153731.1:p.Thr453=, NP_057167.2:p.Thr453=, NP_149421.2:p.Thr420=, XM_005248649.1:c.1359G>A, XM_005248650.1:c.1359G>A, XM_005248650.3:c.1359G>A, XM_005248651.1:c.1260G>A, XM_005248652.1:c.1176G>A, XM_006715330.2:c.1359G>A, XM_011535424.1:c.1359G>A, XM_011535425.1:c.1359G>A, XM_011535426.1:c.1359G>A, XM_011535427.1:c.1359G>A, XM_011535428.1:c.1359G>A, XP_005248706.1:p.Thr453=, XP_005248707.1:p.Thr453=, XP_005248708.1:p.Thr420=, XP_005248709.1:p.Thr392=, XP_006715393.1:p.Thr453=, XP_011533726.1:p.Thr453=, XP_011533727.1:p.Thr453=, XP_011533728.1:p.Thr453=, XP_011533729.1:p.Thr453=, XP_011533730.1:p.Thr453=, rs17264339, rs3173203, rs386513644, rs56973242
C > T
SNP
T453T
No VIP available No Clinical Annotations available VA
rs12970134 NC_000018.10:g.60217517G>A, NC_000018.9:g.57884750G>A, rs60401193
G > A
SNP
No VIP available CA VA
rs1799732 NC_000011.10:g.113475529_113475530insG, NC_000011.9:g.113346251_113346252insG, NG_008841.1:g.4750_4751insC, NM_000795.3:c.-486_-485insC, NM_016574.3:c.-486_-485insC, XM_005271425.1:c.-32+128_-32+129insC, XR_948023.1:n.528_529insC, rs143987432, rs144707848, rs72523179, rs72566141
- > G
indel
No VIP available CA VA
rs1800497 NC_000011.10:g.113400106G>A, NC_000011.9:g.113270828G>A, NG_012976.1:g.17316G>A, NM_178510.1:c.2137G>A, NP_848605.1:p.Glu713Lys, XM_011542736.1:c.2170G>A, XM_011542737.1:c.2140G>A, XM_011542738.1:c.1948G>A, XP_011541038.1:p.Glu724Lys, XP_011541039.1:p.Glu714Lys, XP_011541040.1:p.Glu650Lys, rs117686243, rs4134623, rs4245144, rs59538675
G > A
SNP
E713K
No VIP available No Clinical Annotations available VA
rs1801028 NC_000011.10:g.113412762G>C, NC_000011.9:g.113283484G>C, NG_008841.1:g.67518C>G, NM_000795.3:c.932C>G, NM_016574.3:c.845C>G, NP_000786.1:p.Ser311Cys, NP_057658.2:p.Ser282Cys, XM_005271425.1:c.932C>G, XM_005271426.1:c.929C>G, XP_005271482.1:p.Ser311Cys, XP_005271483.1:p.Ser310Cys, rs4134622
G > C
SNP
S311C
No VIP available No Clinical Annotations available VA
rs2005976 NC_000006.11:g.15650802C>T, NC_000006.12:g.15650571C>T, NG_009309.1:g.17470G>A, NM_001271667.1:c.-83+742G>A, NM_001271668.1:c.110+1516G>A, NM_001271669.1:c.56+12243G>A, NM_032122.4:c.161+742G>A, NM_183040.2:c.161+742G>A, NR_036448.1:n.489+742G>A, XM_005249447.1:c.122+742G>A, XM_005249447.3:c.122+742G>A, XM_011514936.1:c.71+1516G>A, rs2619527
C > T
SNP
No VIP available No Clinical Annotations available VA
rs2304865 NC_000004.11:g.187525363C>G, NC_000004.12:g.186604209C>G, NM_005245.3:c.10548+168G>C, XM_005262834.1:c.10548+168G>C, XM_005262834.2:c.10548+168G>C, XM_005262835.1:c.10548+168G>C, XM_006714139.2:c.10548+168G>C, rs52800791, rs59912924
C > G
SNP
No VIP available No Clinical Annotations available VA
rs2306987 NC_000004.11:g.187516655T>A, NC_000004.12:g.186595501T>A, NM_005245.3:c.13138+188A>T, XM_005262834.1:c.13138+188A>T, XM_005262834.2:c.13138+188A>T, XM_005262835.1:c.13138+188A>T, XM_006714139.2:c.13138+188A>T, rs17692394
T > A
SNP
No VIP available No Clinical Annotations available VA
rs2306990 NC_000004.11:g.187518976C>T, NC_000004.12:g.186597822C>T, NM_005245.3:c.12258-30G>A, XM_005262834.1:c.12258-30G>A, XM_005262834.2:c.12258-30G>A, XM_005262835.1:c.12258-30G>A, XM_006714139.2:c.12258-30G>A
C > T
SNP
No VIP available No Clinical Annotations available VA
rs2391191 NC_000013.10:g.106119446G>A, NC_000013.11:g.105467097G>A, NG_012694.1:g.6231G>A, NM_001161812.1:c.-105G>A, NM_001161814.1:c.-125G>A, NM_172370.4:c.89G>A, NP_758958.3:p.Arg30Lys, NR_040247.1:n.506-677C>T, XM_005254042.1:c.89G>A, XP_005254099.1:p.Arg30Lys, rs52812974, rs59455029
G > A
SNP
R30K
No VIP available No Clinical Annotations available VA
rs2619522 NC_000006.11:g.15653649A>C, NC_000006.12:g.15653418A>C, NG_009309.1:g.14623T>G, NM_001271667.1:c.-232-1278T>G, NM_001271668.1:c.57-1278T>G, NM_001271669.1:c.56+9396T>G, NM_032122.4:c.57-1278T>G, NM_183040.2:c.57-1278T>G, NR_036448.1:n.385-1278T>G, XM_005249447.1:c.18-1278T>G, XM_005249447.3:c.18-1278T>G, XM_011514936.1:c.18-1278T>G, rs59992850
A > C
SNP
No VIP available No Clinical Annotations available VA
rs2637777 NC_000004.11:g.187525020A>C, NC_000004.12:g.186603866A>C, NM_005245.3:c.10660T>G, NP_005236.2:p.Ser3554Ala, XM_005262834.1:c.10660T>G, XM_005262834.2:c.10660T>G, XM_005262835.1:c.10660T>G, XM_006714139.2:c.10660T>G, XP_005262891.1:p.Ser3554Ala, XP_005262892.1:p.Ser3554Ala, XP_006714202.1:p.Ser3554Ala, rs17635884, rs3733404, rs52812769, rs57359486
A > C
SNP
S3554A
No VIP available No Clinical Annotations available VA
rs3213207 NC_000006.11:g.15628102T>C, NC_000006.12:g.15627871T>C, NG_009309.1:g.40170A>G, NM_001271667.1:c.-21-396A>G, NM_001271668.1:c.172-396A>G, NM_001271669.1:c.118-396A>G, NM_032122.4:c.223-396A>G, NM_183040.2:c.223-396A>G, NR_036448.1:n.551-396A>G, XM_005249447.1:c.184-396A>G, XM_005249447.3:c.184-396A>G, XM_011514936.1:c.133-396A>G, rs17472692
T > C
SNP
No VIP available CA VA
rs324420 NC_000001.10:g.46870761C>A, NC_000001.11:g.46405089C>A, NG_012195.1:g.15823C>A, NM_001441.2:c.385C>A, NP_001432.2:p.Pro129Thr, XM_005270624.1:c.385C>A, XM_005270625.1:c.385C>A, XP_005270681.1:p.Pro129Thr, XP_005270682.1:p.Pro129Thr, XR_246250.1:n.463C>A, rs57947754
C > A
SNP
P129T
No VIP available CA VA
rs4305746 NC_000006.11:g.132893765G>A, NC_000006.12:g.132572626G>A, NG_016544.1:g.7305G>A, rs61299378, rs7452939
G > A
SNP
No VIP available CA VA
rs489693 NC_000018.10:g.60215554C>A, NC_000018.9:g.57882787C>A, rs1673474
C > A
SNP
No VIP available CA VA
rs6277 NC_000011.10:g.113412737G>A, NC_000011.9:g.113283459G>A, NG_008841.1:g.67543C>T, NM_000795.3:c.957C>T, NM_016574.3:c.870C>T, NP_000786.1:p.Pro319=, NP_057658.2:p.Pro290=, XM_005271425.1:c.957C>T, XM_005271426.1:c.954C>T, XP_005271482.1:p.Pro319=, XP_005271483.1:p.Pro318=, rs1071576, rs1075651, rs17413837, rs3189090
G > A
SNP
P319P
No VIP available No Clinical Annotations available VA
rs6280 NC_000003.11:g.113890815C>T, NC_000003.12:g.114171968C>T, NG_008842.2:g.32440G>A, NM_000796.5:c.25G>A, NM_001282563.2:c.25G>A, NM_001290809.1:c.25G>A, NM_033663.5:c.25G>A, NP_000787.2:p.Gly9Ser, NP_001269492.1:p.Gly9Ser, NP_001277738.1:p.Gly9Ser, NP_387512.3:p.Gly9Ser, XM_005247170.1:c.25G>A, XM_005247171.1:c.25G>A, XM_011512510.1:c.25G>A, XM_011512511.1:c.25G>A, XM_011512512.1:c.25G>A, XP_005247227.1:p.Gly9Ser, XP_005247228.1:p.Gly9Ser, XP_011510812.1:p.Gly9Ser, XP_011510813.1:p.Gly9Ser, XP_011510814.1:p.Gly9Ser, rs117481259, rs324025, rs52792556, rs59703514
C > T
SNP
G9S
No VIP available No Clinical Annotations available VA
rs646749 NC_000018.10:g.60215892G>A, NC_000018.9:g.57883125G>A, rs386602927, rs60191783
G > A
SNP
No VIP available No Clinical Annotations available VA
rs760761 NC_000006.11:g.15651132G>A, NC_000006.12:g.15650901G>A, NG_009309.1:g.17140C>T, NM_001271667.1:c.-83+412C>T, NM_001271668.1:c.110+1186C>T, NM_001271669.1:c.56+11913C>T, NM_032122.4:c.161+412C>T, NM_183040.2:c.161+412C>T, NR_036448.1:n.489+412C>T, XM_005249447.1:c.122+412C>T, XM_005249447.3:c.122+412C>T, XM_011514936.1:c.71+1186C>T, rs58136591
G > A
SNP
VIP No Clinical Annotations available No Variant Annotations available
rs776746 NC_000007.13:g.99270539C>T, NC_000007.14:g.99672916T>C, NG_007938.1:g.12083G=, NG_007938.1:g.12083G>A, NM_000777.4:c.219-237A>G, NM_000777.4:c.219-237G>A, NM_001190484.2:c.219-237A>G, NM_001190484.2:c.219-237G>A, NM_001291829.1:c.-253-1A>G, NM_001291829.1:c.-253-1G>A, NM_001291830.1:c.189-237A>G, NM_001291830.1:c.189-237G>A, NR_033807.2:n.717-1A>G, NR_033807.2:n.717-1G>A, NR_033808.1:n.689-1G>A, NR_033809.1:n.581-237G>A, NR_033810.1:n.689-1G>A, NR_033811.1:n.321-1G>A, NR_033812.1:n.321-1G>A, XM_005250169.1:c.189-237G>A, XM_005250170.1:c.-357-1G>A, XM_005250171.1:c.-253-1G>A, XM_005250172.1:c.-254G>A, XM_005250173.1:c.-331-237G>A, XM_005250198.1:c.806-4288C>T, XM_006715859.2:c.219-237A>G, XM_011515843.1:c.-254A>G, XM_011515844.1:c.-229-237A>G, XM_011515845.1:c.-463-1A>G, XM_011515846.1:c.-331-237A>G, XM_011515847.1:c.-571-1A>G, XR_927383.1:n.344-237A>G, XR_927402.1:n.1466+48736T>C, rs10361242, rs11266830, rs386613022, rs58244770
C > T
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • OPC 31
  • OPC-14597
  • aripiprazole
Trade Names
  • Abilify
  • Abilitat
Brand Mixture Names

PharmGKB Accession Id

PA10026

Type(s):

Drug

Description

Aripiprazole is an atypical antipsychotic medication used for the treatment of schizophrenia. It has also recently received FDA approval for the treatment of acute manic and mixed episodes associated with bipolar disorder. Aripiprazole appears to mediate its antipsychotic effects primarily by partial agonism at the D2 receptor. In addition to partial agonist activity at the D2 receptor, aripiprazole is also a partial agonist at the 5-HT1A receptor, and like the other atypical antipsychotics, aripiprazole displays an antagonist profile at the 5-HT2A receptor. Aripiprazole has moderate affinity for histamine and alpha adrenergic receptors, and no appreciable affinity for cholinergic muscarinic receptors.

Source: Drug Bank

Pharmacogenetics

Pharmacokinetics

Aripirazole is metabolized extensively in the liver primarily by CYP3A4 and CYP2D6 [Articles:15517848, 17164689]. The major metabolite is dehydroaripiprazole, which contributes to overall activity of the drug [Article:15220010]. CYP2D6 poor metabolizers undergo approximately an 80% increase in aripiprazole plasma concentrations and a 30% decrease in dehydroaripiprazole plasma concentrations Abilify (aripiprazole) package insert. The aripiprazole brain concentration was altered in P-glycoprotein (ABCB1) deficient mice, but deficiency of ABCB1 did not result in significantly altered plasma drug concentrations [Article:19239981].

Pharmacodynamics

Aripiprazole is an atypical antipsychotic drugs. It acts as a partial agonist of dopamine D2 receptors (DRD2) [Articles:14998222, 15019558]. Aripiprazole is also an antagonist at serotonin 2A receptors (HTR2A) and an agonist at serotonin 1A receptors (HTR1A)[Article:14998222]. Additionally, aripiprazole is an antagonist at alpha1 adrenergic receptors. It also exhibits high affinity for dopamine D3 receptors (DRD3), moderate affinity for dopamine D4 receptor (DRD4(, HTR2C, HTR7, and histamine H1 receptors (HRH1) [Article:14998222].

In in vitro studies, aripiprazole was associated with increased brain-derived neurotrophic factor (BDNF) promoter activity at a dose of 10 microM and an increase in levels of glycogen synthase kinase 3 beta (GSK3B) phosphorylation and B cell lymphoma protein 2 (BCL2) in aripiprazole-treated cells [Article:19196496]. Aripiprazole showed marked partial agonist properties for extracellular signal-regulated kinase 1/2 (MAPK3, MAPK1) phosphorylation in CHO cell lines stably expressing the human DRD3 [Article:17588617].

Pharmacogenomics

Polymorphisms in the DRD2 and ANKK1 genes were investigated in association with aripiprazole efficacy in schizophrenic patients [Articles:18926547, 18786813, 18192895]. An in vitro pharmacogenetic study showed that several variants in the HTR2A gene were associated with changes in the potency of four atypical antipsychotic drugs (aripiprazole, clozapine, quetiapine, and risperidone) at the cellular level [Article:20097665]. The role of d-amino acid oxidase activator (DAOA) gene variants on the response to aripiprazole was investigated in a small study in 86 Korean schizophrenia patients [Article:20471098]. No association was found between rs2306987, rs2306990, rs2637777, and rs2304865 in FAT tumor suppressor homolog 1 (FAT1) gene and efficacy and tolerability of aripiprazole [Article:19893579].

Source: PharmGKB

Indication

For the treatment of schizophrenia and related psychotic disorders.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Aripiprazole's antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia.

Source: Drug Bank

Pharmacology

Aripiprazole is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Aripiprazole is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Aripiprazole acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Aripiprazole. Aripiprazole's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Aripiprazole's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.

Source: Drug Bank

Food Interaction

Avoid alcohol (possible additive effect to CNS).|Food has no significant effect on absorption.|Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic.

Source: Drug Bank

Protein Binding

>99%

Source: Drug Bank

Half-Life

75-146 hours

Source: Drug Bank

Route of Elimination

Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces.

Source: Drug Bank

Volume of Distribution

  • 4.9 L/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C23H27Cl2N3O2

Source: Drug Bank

Isomeric SMILES

c1cc(c(c(c1)Cl)Cl)N2CCN(CC2)CCCCOc3ccc4c(c3)NC(=O)CC4

Source: OpenEye

Canonical SMILES

ClC1=CC=CC(N2CCN(CCCCOC3=CC4=C(CCC(=O)N4)C=C3)CC2)=C1Cl

Source: Drug Bank

Average Molecular Weight

448.385

Source: Drug Bank

Monoisotopic Molecular Weight

447.148032537

Source: Drug Bank

SMILES

ClC1=CC=CC(N2CCN(CCCCOC3=CC4=C(CCC(=O)N4)C=C3)CC2)=C1Cl

Source: Drug Bank

InChI String

InChI=1S/C23H27Cl2N3O2/c24-19-4-3-5-21(23(19)25)28-13-11-27(12-14-28)10-1-2-15-30-18-8-6-17-7-9-22(29)26-20(17)16-18/h3-6,8,16H,1-2,7,9-15H2,(H,26,29)

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ADRA1A (source: Drug Bank)
ADRA1B (source: Drug Bank)
ADRA2A (source: Drug Bank)
ADRA2B (source: Drug Bank)
ADRA2C (source: Drug Bank)
CHRM1 (source: Drug Bank)
CHRM2 (source: Drug Bank)
CHRM3 (source: Drug Bank)
CHRM4 (source: Drug Bank)
CHRM5 (source: Drug Bank)
DRD1 (source: Drug Bank)
DRD2 (source: Drug Bank)
DRD3 (source: Drug Bank)
DRD4 (source: Drug Bank)
DRD5 (source: Drug Bank)
HRH1 (source: Drug Bank)
HTR1A (source: Drug Bank)
HTR1B (source: Drug Bank)
HTR1D (source: Drug Bank)
HTR1E (source: Drug Bank)
HTR2A (source: Drug Bank)
HTR2C (source: Drug Bank)
HTR3A (source: Drug Bank)
HTR6 (source: Drug Bank)
HTR7 (source: Drug Bank)

Drug Interactions

Interaction Description
aripiprazole - carbamazepine Carbamazepine decreases the effect of aripiprazole (source: Drug Bank)
aripiprazole - carbamazepine Carbamazepine decreases the effect of aripiprazole (source: Drug Bank)
aripiprazole - itraconazole The imidazole increases the effect of aripiprazole (source: Drug Bank)
aripiprazole - itraconazole The imidazole increases the effect of aripiprazole (source: Drug Bank)
aripiprazole - ketoconazole The imidazole increases the effect of aripiprazole (source: Drug Bank)
aripiprazole - ketoconazole The imidazole increases the effect of aripiprazole (source: Drug Bank)
aripiprazole - quinidine Quinidine increases the effect and toxicity of aripiprazole (source: Drug Bank)
aripiprazole - quinidine Quinidine increases the effect and toxicity of aripiprazole (source: Drug Bank)
aripiprazole - quinidine Quinidine increases the effect and toxicity of aripiprazole (source: Drug Bank)
carbamazepine - aripiprazole Decreases the effect of aripiprazole (source: Drug Bank)
carbamazepine - aripiprazole Decreases the effect of aripiprazole (source: Drug Bank)
itraconazole - aripiprazole The imidazole increases the effect of aripiprazole (source: Drug Bank)
itraconazole - aripiprazole The imidazole increases the effect of aripiprazole (source: Drug Bank)
ketoconazole - aripiprazole The imidazole increases the effect of aripiprazole (source: Drug Bank)
ketoconazole - aripiprazole The imidazole increases the effect of aripiprazole (source: Drug Bank)
quinidine - aripiprazole Quinidine increases the effect and toxicity of aripiprazole (source: Drug Bank)
quinidine - aripiprazole Quinidine increases the effect and toxicity of aripiprazole (source: Drug Bank)
tacrine - aripiprazole Tacrine, a central acetylcholinesterase inhibitor, may augment the central neurotoxic effect of antipsychotics such as Aripiprazole. Monitor for extrapyramidal symptoms. (source: Drug Bank)
telithromycin - aripiprazole Telithromycin may reduce clearance of Aripiprazole. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Aripiprazole if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
tetrabenazine - aripiprazole May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. (source: Drug Bank)
trazodone - aripiprazole The 2D6 inhibitor, Trazodone, may increase the efficacy of Aripiprazole by decreasing Ariprazole metabolism and clearance. Monitor for changes in Aripiprazole efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
trazodone - aripiprazole The 2D6 inhibitor, Trazodone, may increase the efficacy of Aripiprazole by decreasing Ariprazole metabolism and clearance. Monitor for changes in Aripiprazole efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
triprolidine - aripiprazole The CNS depressants, Triprolidine and Aripiprazole, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
triprolidine - aripiprazole The CNS depressants, Triprolidine and Aripiprazole, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
voriconazole - aripiprazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of aripiprazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of aripiprazole if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to aripiprazole: 38

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genotype and co-medication dependent CYP2D6 metabolic activity: effects on serum concentrations of aripiprazole, haloperidol, risperidone, paliperidone and zuclopenthixol. European journal of clinical pharmacology. 2015. Lisbeth Patteet, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical applications of CYP genotyping in psychiatry. Journal of neural transmission (Vienna, Austria : 1996). 2015. Spina Edoardo, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Metabolic side effects and pharmacogenetics of second-generation antipsychotics in children. Pharmacogenomics. 2015. Devlin Angela M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Serum concentrations of risperidone and aripiprazole in subgroups encoding CYP2D6 intermediate metabolizer phenotype. Therapeutic drug monitoring. 2014. Hendset Magnhild, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
MC4R rs489693: a clinical risk factor for second generation antipsychotic-related weight gain?. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 2013. Czerwensky Fabian, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies. Translational psychiatry. 2013. Nurmi E L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain. Archives of general psychiatry. 2012. Malhotra Anil K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenetics and genomics. 2012. Lamba Jatinder, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism: effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine. European journal of clinical pharmacology. 2012. Azuma Junichi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymorphisms of the LEP, LEPR and HTR2C gene: obesity and BMI change in patients using antipsychotic medication in a naturalistic setting. Pharmacogenomics. 2011. Gregoor Jochem G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-beta. The pharmacogenomics journal. 2010. Pavan C, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. Journal of clinical psychopharmacology. 2010. Monteleone Palmiero, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Influence of DAOA gene variants on antipsychotic response after switch to aripiprazole. Psychiatry research. 2010. Pae Chi-Un, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis. The American journal of psychiatry. 2010. Zhang Jian-Ping, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in Schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2010. Tiwari Arun K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
No influence of FAT polymorphisms in response to aripiprazole. Journal of human genetics. 2010. Pae Chi-Un, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
No influence of DTNBP1 polymorphisms on the response to aripiprazole. Neuropsychobiology. 2010. Pae Chi-Un, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influence of TAAR6 polymorphisms on response to aripiprazole. Progress in neuro-psychopharmacology & biological psychiatry. 2009. Serretti Alessandro, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ADME pharmacogenetics: current practices and future outlook. Expert opinion on drug metabolism & toxicology. 2009. Grossman Iris. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Effects of the DRD3 Ser9Gly polymorphism on aripiprazole efficacy in schizophrenic patients as modified by clinical factors. Progress in neuro-psychopharmacology & biological psychiatry. 2009. Chen Shih-Fen, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients. Journal of psychiatric research. 2009. Shen Yu-Chih, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Movement disorders associated with aripiprazole use: a case series. The International journal of neuroscience. 2009. Hall Deborah A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia. Pharmacogenomics. 2008. Ikeda Masashi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Taq1A polymorphism in the dopamine D2 receptor gene predicts brain metabolic response to aripiprazole in healthy male volunteers. Pharmacogenetics and genomics. 2008. Kim Euitae, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Impact of the CYP2D6 genotype on steady-state serum concentrations of aripiprazole and dehydroaripiprazole. European journal of clinical pharmacology. 2007. Hendset Magnhild, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacokinetics of aripiprazole, a new antipsychotic, following oral dosing in healthy adult Japanese volunteers: influence of CYP2D6 polymorphism. Drug metabolism and pharmacokinetics. 2007. Kubo Masanori, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
The relationship between the therapeutic response to risperidone and the dopamine D2 receptor polymorphism in Chinese schizophrenia patients. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 2007. Xing Qinghe, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. The American journal of psychiatry. 2006. Lencz Todd, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Association study of 12 polymorphisms spanning the dopamine D(2) receptor gene and clozapine treatment response in two treatment refractory/intolerant populations. Psychopharmacology. 2005. Hwang Rudi, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neuroscience letters. 2005. Wu Shengnan, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
The -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter region is associated with anxiolytic and antidepressive effects during treatment with dopamine antagonists in schizophrenic patients. Pharmacogenetics. 2001. Suzuki A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response. Pharmacogenetics. 1998. Arranz M J, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Functional polymorphism of -141C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia. Psychiatry research. 1998. Ohara K, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
59148-013-15
DrugBank:
DB01238
ChEBI:
31236
KEGG Compound:
C12564
KEGG Drug:
D01164
PubChem Compound:
60795
PubChem Substance:
46505745
582954
IUPHAR Ligand:
34
ChemSpider:
54790
Therapeutic Targets Database:
DAP000076
FDA Drug Label at DailyMed:
c040bd1d-45b7-49f2-93ea-aed7220b30ac

Clinical Trials

These are trials that mention aripiprazole and are related to either pharmacogenetics or pharmacogenomics.

No trials found.

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Sources for PharmGKB drug information: DrugBank, PubChem.