CYP1A2*F Polymorphism contributes at least partially to the Variability of Plasma Levels of Dehydroaripiprazole, an active Metabolite of Aripiprazole, in Schizophrenic Patients

Takeshi Suzuki; Goyo Nagai; Kazuo Mihara; Yoko Tomori; Shoko Kagawa; Akifumi Nakamura; Kenji Nemoto; Tsuyoshi Kondo

doi:10.2174/0118723128246698230921095141

CYP1A2*F Polymorphism contributes at least partially to the Variability of Plasma Levels of Dehydroaripiprazole, an active Metabolite of Aripiprazole, in Schizophrenic Patients

Drug Metab Bioanal Lett. 2023 Oct 6. doi: 10.2174/0118723128246698230921095141. Online ahead of print.

Authors

Takeshi Suzuki^{1

2}, Goyo Nagai¹, Kazuo Mihara^{1

3}, Yoko Tomori¹, Shoko Kagawa¹, Akifumi Nakamura¹, Kenji Nemoto¹, Tsuyoshi Kondo¹

Affiliations

¹ Departments of Neuropsychiatry, Kyoto, Japan.
² Pharmacy, Graduate School of Medicine, Kyoto, Japan.
³ Uji Oubaku Hospital, Kyoto, Japan.

PMID: 37855290
DOI: 10.2174/0118723128246698230921095141

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 metabolism 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.

Keywords: Aripiprazole; CYP1A2 polymorphism; dehydroaripiprazole; metabolism.