Effects of genetic polymorphisms of CYP2D6, CYP3A5, and ABCB1 on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia.
Abstract | BACKGROUND: METHODS: RESULTS: The mean concentration/dose ratios of aripiprazole and the sum of aripiprazole and dehydroaripiprazole were significantly higher in patients with 1 (P < 0.01 and P < 0.01) or 2 (P < 0.001 and P < 0.05) mutated alleles for CYP2D6 than in those without mutated alleles. No differences were found in the values of dehydroaripiprazole among CYP2D6 genotypes. There were no differences in the values of aripiprazole, dehydroaripiprazole, and the sum of the 2 compounds among CYP3A5 or the 2 ABCB1 variants. Multiple regression analyses including these polymorphisms, age, gender, and smoking habit showed that only the number of mutated alleles for CYP2D6 was correlated with mean concentration/dose ratios of aripiprazole [standardized partial correlation coefficients (beta) = 0.420, P < 0.001] and the sum of the 2 compounds (standardized beta = 0.335, P < 0.01). CONCLUSIONS: The findings of this study suggest that CYP2D6 genotypes play an important role in controlling steady-state plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole in Asian subjects, whereas CYP3A5 and ABCB1 genotypes seemed unlikely to have an impact.
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Authors | Takeshi Suzuki, Kazuo Mihara, Akifumi Nakamura, Shoko Kagawa, Goyo Nagai, Kenji Nemoto, Tsuyoshi Kondo |
Journal | Therapeutic drug monitoring
(Ther Drug Monit)
Vol. 36
Issue 5
Pg. 651-5
(Oct 2014)
ISSN: 1536-3694 [Electronic] United States |
PMID | 24682161
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ABCB1 protein, human
- ATP Binding Cassette Transporter, Subfamily B
- Antipsychotic Agents
- Piperazines
- Quinolones
- dehydroaripiprazole
- Aripiprazole
- CYP3A5 protein, human
- Cytochrome P-450 CYP2D6
- Cytochrome P-450 CYP3A
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Topics |
- ATP Binding Cassette Transporter, Subfamily B
(genetics, metabolism)
- Adult
- Antipsychotic Agents
(blood, pharmacokinetics, therapeutic use)
- Aripiprazole
- Asian People
- Cytochrome P-450 CYP2D6
(genetics, metabolism)
- Cytochrome P-450 CYP3A
(genetics, metabolism)
- Female
- Genotype
- Humans
- Male
- Middle Aged
- Piperazines
(blood, metabolism, pharmacokinetics, therapeutic use)
- Polymorphism, Genetic
- Quinolones
(blood, metabolism, pharmacokinetics, therapeutic use)
- Schizophrenia
(drug therapy)
- Young Adult
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