About this pathway
Background
Aripiprazole is an atypical antipsychotic used in the treatment of adults and adolescents with schizophrenia or schizoaffective disorder and children and adolescents with bipolar disorder [Articles:15257633, 21359119]. Aripiprazole is also FDA-approved for use in children and adolescents with autism age 6-17 [Article:21359119]. A long acting injectable prodrug aripiprazole lauroxil is also approved for treatment of schizophrenia [Article:28350572].
Metabolism
Aripiprazole lauroxil is metabolized to N-hydroxymethyl aripiprazole by esterases (no specific candidates documented)[Article:28350572]. It then undergoes non-enzymatic hydrolysis to aripiprazole [Article:28350572].
Aripiprazole is then extensively metabolized in the liver via N-dealkylation, hydroxylation or dehydrogenation pathways [Article:15257633]. CYP3A and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation, and N-dealkylation is catalyzed by CYP3A4 [Article:21476873]. Dehydroaripiprazole (OPC-14857) is the main metabolite in humans [Article:21476873]. Dehydroaripiprazole has similar pharmacological properties to aripiprazole; therefore, the sum of the parent drug and its dehydro-metabolite is often used in therapeutic measurement [Article:30604050].
Transport
Aripiprazole is a substrate for ABCB1 and variants have been shown to influence drug clearance [Articles:29325225, 29443543]. Aripiprazole and dehydroaripiprazole are inhibitors of ABCB1 (MDR1) and ABCG2 (BCRP) [Article:22847220].
Reactions & interactions (17)
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Biochemical Reaction
aripiprazole → dehydroaripiprazole
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Biochemical Reaction
aripiprazole → aripiprazole metabolite DM-1451
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Biochemical Reaction
aripiprazole → 1-(2,3-dichlorophenyl)piperazine
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Biochemical Reaction
N-hydroxymethyl aripiprazole → aripiprazole + formaldehyde
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Biochemical Reaction
aripiprazole lauroxil → N-hydroxymethyl aripiprazole + lauric acid
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
ABCB1 → Transport
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Inhibition
dehydroaripiprazole → ABCG2
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Inhibition
aripiprazole → ABCB1
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Inhibition
dehydroaripiprazole → ABCB1
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Inhibition
aripiprazole → ABCG2
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Transport
aripiprazole → aripiprazole
Edit history (3)
- 2021-07-15 Create
- 2025-02-21 Update fixed typo
- 2026-02-12 Update Updated watermark and image map.