Title:CYP1A2*F Polymorphism Contributes at Least Partially to the Variability
of Plasma Levels of Dehydroaripiprazole, an Active Metabolite of
Aripiprazole, in Schizophrenic Patients
Volume: 17
Issue: 1
Author(s): Takeshi Suzuki, Goyo Nagai, Kazuo Mihara*, Yoko Tomori, Shoko Kagawa, Akifumi Nakamura, Kenji Nemoto and Tsuyoshi Kondo
Affiliation:
- Departments of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
- Uji Oubaku Hospital, Kyoto, Japan
Keywords:
Aripiprazole, dehydroaripiprazole, metabolism, CYP1A2 polymorphism, schizophrenia, polymerase chain reac-tion.
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.
