1. CYP1A2*F Polymorphism Contributes at Least Partially to the Variability of Plasma Levels of Dehydroaripiprazole, an Active Metabolite of Aripiprazole, in Schizophrenic Patients.
- Author
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Suzuki T, Nagai G, Mihara K, Tomori Y, Kagawa S, Nakamura A, Nemoto K, and Kondo T
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Polymorphism, Genetic genetics, Asian People genetics, Genotype, Aripiprazole blood, Aripiprazole pharmacokinetics, Schizophrenia drug therapy, Schizophrenia genetics, Schizophrenia blood, Cytochrome P-450 CYP1A2 genetics, Cytochrome P-450 CYP1A2 metabolism, Piperazines blood, Piperazines pharmacokinetics, Piperazines therapeutic use, Quinolones blood, Quinolones pharmacokinetics, Antipsychotic Agents blood, Antipsychotic Agents pharmacokinetics, Antipsychotic Agents therapeutic use
- Abstract
Aim: The relationship between CYP1A2 polymorphisms and the steady-state plasma levels of aripiprazole and its active metabolite, dehydroaripiprazole, were investigated in Japanese schizophrenic patients., Background: It has been implied that cytochrome P450 (CYP) 1A2 may play a role in the metabo-lism of aripiprazole. Genetic variations in the CYP1A2 gene have been reported., Objective: The authors investigated the relationship between 2 CYP1A2 polymorphisms, CYP1A2*C (-3860G>A) and CYP1A2*F (-163C>A) , and the steady-state plasma levels/dose (C/D) ratios of aripiprazole and dehydroaripiprazole in Japanese schizophrenic patients., Methods: All 89 subjects (46 males and 43 females) had been receiving 2 fixed daily doses of aripiprazole (24 mg; n=56 and 12 mg: n=33) for more than 2 weeks. No other drugs were used except flunitrazepam and biperiden. The plasma drug levels were determined by LC/MS/MS. These CYP1A2 polymorphisms were detected using polymerase chain reaction analysis., Results: The mean C/D ratios of dehydroaripiprazole were significantly (P < 0.05) lower in patients with the A/A allele of CYP1A2*F than in those without the allele. No differences were found in the values of aripiprazole and the combination of aripiprazole and dehydroaripiprazole among the CYP1A2 *F genotype. There were no differences in the values of aripiprazole, dehydroaripiprazole, or the combination of the 2 compounds among the CYP1A2 *C genotype. The absence of the A allele of CYP1A2 *F was correlated with the mean C/D ratios of dehydroaripiprazole (standardized partial correlation coefficient = 0.276, P < 0.01) by multiple regression analysis., Conclusion: The findings of this study suggest that the CYP1A2 *F polymorphism contributes at least partially to the variability in the steady-state plasma levels of dehydroaripiprazole., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
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