Influence of CYP2D6 gene polymorphisms on the pharmacokinetics of aripiprazole in healthy Chinese subjects

Author:

Zhang Xiaodan1ORCID,Liu Chengquan2,Zhou Shuang1,Xie Ran1,He Xu1,Wang Zhiqi1,Yi Honghong2,Shu You2,Wang Zining1,Hu Kun1,Ma Lingyue1,Cui Yimin13,Zhao Xia1ORCID,Xiang Jin4

Affiliation:

1. Department of Pharmacy, Base for Clinical Trial, Peking University First Hospital, Beijing 100034, China

2. Department of Clinical Pharmacology, The First Affiliated Hospital of Hunan University of Medicine, Huaihua, Hunan 418000, China

3. Institute of Clinical Pharmacology, Peking University, No. 38, Xue Yuan Street, Haidian District, Beijing 100191, China

4. GCP Center, West China Hospital, Sichuan University, Chengdu 610041, China

Abstract

Background: Pharmacogenetics study was added into 2 bioequivalence trials of aripiprazole. The correlation between CYP2D6 polymorphisms and aripiprazole pharmacokinetics (PK) was analyzed. Materials & methods: A total of 140 subjects were included. A total of 26 CYP2D6 gene alleles were detected. The plasma concentration of aripiprazole was measured by liquid chromatography-tandem mass spectrometry. SPSS Statistics 21 was used to analyze the correlation between CYP2D6 polymorphisms and aripiprazole PK parameters. Results: All of the four PK parameters were significantly influenced by CYP2D6 rs1058164 and rs28371699. t1/2 and area under the concentration-time curve exhibited significant difference between CYP2D6 extensive metabolizers and intermediate metabolizers. Conclusion: Aripiprazole PK was greatly influenced by CYP2D6. Attention should be paid to the possible dose adjustment for CYP2D6 intermediate metabolizer population when the drug is used in Chinese patients.

Funder

National Science and Technology Major Projects for “Major New Drugs Innovation and Development” of China

Grants from the National Key R&D Program of China

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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