Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders
Abstract Background Aripiprazole (ARI) is the first-line treatment for tic disorders (TD). Cytochrome P450(CYP)2D6 (CYP2D6) and ATP-binding cassette, sub-family B, member 1 (ABCB1) transporter are involved in the metabolism of ARI. However, whether CYP2D6 and ABCB1 genetic polymorphisms influence cl...
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2025-07-01
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| Series: | BMC Pediatrics |
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| Online Access: | https://doi.org/10.1186/s12887-025-05856-6 |
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| author | Yingying Xin Liuliu Gao Sichan Li Jun Wang Chen Chen Yali Tuo Gang Nie Ruizhen Li Dan Sun Yongli Fu Yang Wang Zhisheng Liu |
| author_facet | Yingying Xin Liuliu Gao Sichan Li Jun Wang Chen Chen Yali Tuo Gang Nie Ruizhen Li Dan Sun Yongli Fu Yang Wang Zhisheng Liu |
| author_sort | Yingying Xin |
| collection | DOAJ |
| description | Abstract Background Aripiprazole (ARI) is the first-line treatment for tic disorders (TD). Cytochrome P450(CYP)2D6 (CYP2D6) and ATP-binding cassette, sub-family B, member 1 (ABCB1) transporter are involved in the metabolism of ARI. However, whether CYP2D6 and ABCB1 genetic polymorphisms influence clinical efficacy and pharmacokinetics of ARI remains unclear. Methods CYP2D6 and ABCB1 genotyping were performed. Pharmacokinetic parameters of ARI and its metabolite dehydroaripiprazole (DARI) were derived using a previously established population pharmacokinetic model. Drug response after ARI administration was evaluated based on reduction rate of Yale Global Tic Severity Scale score (YGTSS). Results Steady-state DARI/ARI metabolic ratios (MRs) of AUC0 − t, Cmin and Cmax were significantly associated with CYP2D6 rs1135840, CYP2D6 rs5030865, CYP2D6 rs1058164, CYP2D6 rs28371702, CYP2D6 rs1065852 and CYP2D6 rs1080989. The clearance (CL) of ARI was influenced by CYP2D6 rs1135840, CYP2D6 rs5030865, and CYP2D6 rs1080989. CYP2D6 rs16947, CYP2D6 rs29001518 and CYP2D6 rs1080985 were correlated with the CL of DARI. The CYP2D6 rs5030865 polymorphism was associated with volume of distribution (V) of DARI. The ABCB1 C3435T (rs1045642) polymorphism influenced the V of ARI. CYP2D6 rs1065852 and CYP2D6 rs1080989 were significantly associated with drug response of ARI. Conclusion Pharmacokinetic parameters of ARI were correlated with CYP2D6 polymorphisms. CYP2D6 genotyping was recommended in ARI therapy. Further researches are required to elucidate the role of ABCB1 polymorphisms in ARI metabolism. |
| format | Article |
| id | doaj-art-8775ac75ad5a40e0b4f5b711bd2d2cc6 |
| institution | DOAJ |
| issn | 1471-2431 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pediatrics |
| spelling | doaj-art-8775ac75ad5a40e0b4f5b711bd2d2cc62025-08-20T03:04:17ZengBMCBMC Pediatrics1471-24312025-07-0125111010.1186/s12887-025-05856-6Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disordersYingying Xin0Liuliu Gao1Sichan Li2Jun Wang3Chen Chen4Yali Tuo5Gang Nie6Ruizhen Li7Dan Sun8Yongli Fu9Yang Wang10Zhisheng Liu11Department of Child Health, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Child Health, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Neurology, Tongji Medical College, Wuhan Children’s Hospital, Huazhong University of Science & TechnologyDepartment of Pharmacy, Wuhan Mental Health Center, Tongji Medical College, Huazhong University of Science & TechnologyOffice of Clinical Trial Institution, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Neurology, Tongji Medical College, Wuhan Children’s Hospital, Huazhong University of Science & TechnologyAbstract Background Aripiprazole (ARI) is the first-line treatment for tic disorders (TD). Cytochrome P450(CYP)2D6 (CYP2D6) and ATP-binding cassette, sub-family B, member 1 (ABCB1) transporter are involved in the metabolism of ARI. However, whether CYP2D6 and ABCB1 genetic polymorphisms influence clinical efficacy and pharmacokinetics of ARI remains unclear. Methods CYP2D6 and ABCB1 genotyping were performed. Pharmacokinetic parameters of ARI and its metabolite dehydroaripiprazole (DARI) were derived using a previously established population pharmacokinetic model. Drug response after ARI administration was evaluated based on reduction rate of Yale Global Tic Severity Scale score (YGTSS). Results Steady-state DARI/ARI metabolic ratios (MRs) of AUC0 − t, Cmin and Cmax were significantly associated with CYP2D6 rs1135840, CYP2D6 rs5030865, CYP2D6 rs1058164, CYP2D6 rs28371702, CYP2D6 rs1065852 and CYP2D6 rs1080989. The clearance (CL) of ARI was influenced by CYP2D6 rs1135840, CYP2D6 rs5030865, and CYP2D6 rs1080989. CYP2D6 rs16947, CYP2D6 rs29001518 and CYP2D6 rs1080985 were correlated with the CL of DARI. The CYP2D6 rs5030865 polymorphism was associated with volume of distribution (V) of DARI. The ABCB1 C3435T (rs1045642) polymorphism influenced the V of ARI. CYP2D6 rs1065852 and CYP2D6 rs1080989 were significantly associated with drug response of ARI. Conclusion Pharmacokinetic parameters of ARI were correlated with CYP2D6 polymorphisms. CYP2D6 genotyping was recommended in ARI therapy. Further researches are required to elucidate the role of ABCB1 polymorphisms in ARI metabolism.https://doi.org/10.1186/s12887-025-05856-6CYP2D6ABCB1AripiprazolePharmacokineticsTic disordersEfficacy |
| spellingShingle | Yingying Xin Liuliu Gao Sichan Li Jun Wang Chen Chen Yali Tuo Gang Nie Ruizhen Li Dan Sun Yongli Fu Yang Wang Zhisheng Liu Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders BMC Pediatrics CYP2D6 ABCB1 Aripiprazole Pharmacokinetics Tic disorders Efficacy |
| title | Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders |
| title_full | Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders |
| title_fullStr | Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders |
| title_full_unstemmed | Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders |
| title_short | Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders |
| title_sort | effect of cyp2d6 and abcb1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders |
| topic | CYP2D6 ABCB1 Aripiprazole Pharmacokinetics Tic disorders Efficacy |
| url | https://doi.org/10.1186/s12887-025-05856-6 |
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