ABCB1 基因多态性对 CYP2D6*10/*10 健康受试者利培酮药代动力学的影响。
Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of risperidone in healthy subjects with CYP2D6*10/*10.
机构信息
College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University, Gwangju, Korea.
出版信息
Br J Pharmacol. 2011 Sep;164(2b):433-43. doi: 10.1111/j.1476-5381.2011.01385.x.
Abstract
BACKGROUND AND PURPOSE
The objective of this study was to investigate the combined influence of genetic polymorphisms in ABCB1 and CYP2D6 genes on risperidone pharmacokinetics.
EXPERIMENTAL APPROACH
Seventy-two healthy Korean volunteers receiving a single oral dose of 2 mg risperidone were included in this study.
KEY RESULTS
Significant differences were observed between the ABCB1 3435C>T genotypes for the pharmacokinetic parameters (peak serum concentration) of risperidone and the active moiety (risperidone and its main metabolite, 9-hydroxyrisperidone). There were no significant differences in the area under the serum concentration-time curves of risperidone and the active moiety among the ABCB1 2677G>T/A and 3435C>T genotypes. However, the peak serum concentration and area under the serum concentration-time curves were significantly different among the ABCB1 3435C>T genotypes in CYP2D6*10/*10.
CONCLUSIONS AND IMPLICATIONS
These findings indicate that polymorphisms of ABCB1 3435C>T in individuals with CYP2D6*10/*10, which has low metabolic activity, could play an important role in the potential adverse effects or toxicity of risperidone.
摘要
背景与目的
本研究旨在探讨 ABCB1 和 CYP2D6 基因的遗传多态性对利培酮药代动力学的联合影响。
实验方法
本研究纳入了 72 名接受单剂量 2mg 利培酮口服的健康韩国志愿者。
主要结果
ABCB1 3435C>T 基因型在利培酮和活性部分（利培酮及其主要代谢物 9-羟基利培酮）的药代动力学参数（峰血清浓度）方面存在显著差异。ABCB1 2677G>T/A 和 3435C>T 基因型之间，利培酮和活性部分的血清浓度-时间曲线下面积没有显著差异。然而，在 CYP2D6*10/*10 低代谢活性的个体中，ABCB1 3435C>T 基因型的峰血清浓度和血清浓度-时间曲线下面积有显著差异。
结论和意义
这些发现表明，CYP2D6*10/*10 个体中 ABCB1 3435C>T 的多态性可能在利培酮的潜在不良反应或毒性方面发挥重要作用。
相似文献
1
Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of risperidone in healthy subjects with CYP2D6*10/*10.ABCB1 基因多态性对 CYP2D6*10/*10 健康受试者利培酮药代动力学的影响。
Br J Pharmacol. 2011 Sep;164(2b):433-43. doi: 10.1111/j.1476-5381.2011.01385.x.
2
Population pharmacokinetic analysis of risperidone and 9-hydroxyrisperidone with genetic polymorphisms of CYP2D6 and ABCB1.基于 CYP2D6 和 ABCB1 基因多态性的利培酮和 9-羟基利培酮的群体药代动力学分析。
J Pharmacokinet Pharmacodyn. 2012 Aug;39(4):329-41. doi: 10.1007/s10928-012-9253-5. Epub 2012 May 24.
3
The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone.CYP2D6 和 ABCB1 药物遗传学在利培酮治疗首发精神分裂症药物初治患者中的作用。
Eur J Clin Pharmacol. 2010 Nov;66(11):1109-17. doi: 10.1007/s00228-010-0850-1. Epub 2010 Jun 19.
4
ABCB1 polymorphisms influence steady-state plasma levels of 9-hydroxyrisperidone and risperidone active moiety.ABCB1 多态性影响 9-羟基利培酮和利培酮活性代谢物的稳态血浆水平。
Ther Drug Monit. 2008 Oct;30(5):628-33. doi: 10.1097/FTD.0b013e3181858ca9.
5
Effect of CYP2D6, CYP3A5, and MDR1 genetic polymorphisms on the pharmacokinetics of risperidone and its active moiety.CYP2D6、CYP3A5 和 MDR1 基因多态性对利培酮及其活性代谢物药代动力学的影响。
J Clin Pharmacol. 2010 Jun;50(6):659-66. doi: 10.1177/0091270009347867. Epub 2010 Mar 23.
6
Impact of the ABCB1 gene polymorphism on plasma 9-hydroxyrisperidone and active moiety levels in Japanese patients with schizophrenia.ABCB1 基因多态性对日本精神分裂症患者血浆 9-羟基利培酮和活性代谢物水平的影响。
J Clin Psychopharmacol. 2013 Jun;33(3):411-4. doi: 10.1097/JCP.0b013e31828ecd52.
7
Pharmacokinetics and bioequivalence evaluation of risperidone in healthy male subjects with different CYP2D6 genotypes.利培酮在不同CYP2D6基因型健康男性受试者中的药代动力学及生物等效性评价
Arch Pharm Res. 2006 Jun;29(6):525-33. doi: 10.1007/BF02969428.
8
Effects of CYP2D6, CYP3A5, and ABCB1 gene polymorphisms on the pharmacokinetics of two risperidone long-acting injection microsphere formulations.CYP2D6、CYP3A5 和 ABCB1 基因多态性对两种利培酮长效注射微球制剂药代动力学的影响。
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jul 13;109:110241. doi: 10.1016/j.pnpbp.2020.110241. Epub 2021 Jan 2.
9
ABCB1, ABCG2 and CYP2D6 polymorphism effects on disposition and response to long-acting risperidone.ABCB1、ABCG2 和 CYP2D6 多态性对长效利培酮处置和反应的影响。
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jan 10;104:110042. doi: 10.1016/j.pnpbp.2020.110042. Epub 2020 Jul 17.
10
Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort.基于遗传学的利培酮在精神科队列中的群体药代动力学和药效学
Clin Pharmacokinet. 2015 Dec;54(12):1259-72. doi: 10.1007/s40262-015-0289-8.
引用本文的文献
1
Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations.ABCB1基因多态性对阿立哌唑及去氢阿立哌唑血浆浓度的影响。
Sci Rep. 2025 Jan 9;15(1):1521. doi: 10.1038/s41598-024-84192-8.
2
Exploratory focused pharmacogenetic testing reveals novel markers associated with risperidone pharmacokinetics in Saudi children with autism.探索性重点药物遗传学检测揭示了沙特自闭症儿童中与利培酮药代动力学相关的新标志物。
Front Pharmacol. 2024 Feb 5;15:1356763. doi: 10.3389/fphar.2024.1356763. eCollection 2024.
3
Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone.CYP2D6 多态性对利培酮血药浓度和疗效的影响。
BMC Psychiatry. 2021 Feb 3;21(1):70. doi: 10.1186/s12888-020-03034-9.
4
Genotype-Based Dose Recommendations for Risperidone in Asian People.亚洲人群中基于基因型的利培酮剂量推荐
Front Pharmacol. 2020 Aug 4;11:936. doi: 10.3389/fphar.2020.00936. eCollection 2020.
5
Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and -Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling.利用基于生理的药代动力学模型评估CYP2D6基因多态性对韩国人群中曲马多及其去甲基代谢物药代动力学特征的影响。
Pharmaceutics. 2019 Nov 17;11(11):618. doi: 10.3390/pharmaceutics11110618.
6
Population pharmacokinetic analysis of tramadol and desmethyltramadol with genetic polymorphism of .曲马多和去甲基曲马多的群体药代动力学分析与……的基因多态性
Drug Des Devel Ther. 2019 May 23;13:1751-1761. doi: 10.2147/DDDT.S199574. eCollection 2019.
7
A Prospective Study to Evaluate the Effect of CYP2D6 Polymorphism on Plasma level of Risperidone and its Metabolite in North Indian Patients with Schizophrenia.一项评估CYP2D6基因多态性对北印度精神分裂症患者血浆中利培酮及其代谢物水平影响的前瞻性研究。
Indian J Psychol Med. 2018 Jul-Aug;40(4):335-342. doi: 10.4103/IJPSYM.IJPSYM_83_18.
8
The predictive value of ABCB1, ABCG2, CYP3A4/5 and CYP2D6 polymorphisms for risperidone and aripiprazole plasma concentrations and the occurrence of adverse drug reactions.ABCB1、ABCG2、CYP3A4/5和CYP2D6基因多态性对利培酮和阿立哌唑血药浓度及药物不良反应发生情况的预测价值。
Pharmacogenomics J. 2018 May 22;18(3):422-430. doi: 10.1038/tpj.2017.38. Epub 2017 Jul 18.
9
New Modified UPLC/Tandem Mass Spectrometry Method for Determination of Risperidone and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Dose-Dependent Pharmacokinetic Study in Sprague-Dawley Rats.用于测定血浆中利培酮及其活性代谢物9-羟基利培酮的新型改良超高效液相色谱/串联质谱法：在斯普拉格-道利大鼠剂量依赖性药代动力学研究中的应用
Int J Anal Chem. 2017;2017:1271383. doi: 10.1155/2017/1271383. Epub 2017 May 3.
10
Pharmacogenomic Study Reveals New Variants of Drug Metabolizing Enzyme and Transporter Genes Associated with Steady-State Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Thai Autism Spectrum Disorder Patients.药物基因组学研究揭示了与泰国自闭症谱系障碍患者中利培酮和9-羟基利培酮稳态血药浓度相关的药物代谢酶和转运蛋白基因的新变体。
Front Pharmacol. 2016 Dec 2;7:475. doi: 10.3389/fphar.2016.00475. eCollection 2016.
本文引用的文献
1
The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone.CYP2D6 和 ABCB1 药物遗传学在利培酮治疗首发精神分裂症药物初治患者中的作用。
Eur J Clin Pharmacol. 2010 Nov;66(11):1109-17. doi: 10.1007/s00228-010-0850-1. Epub 2010 Jun 19.
2
Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of levosulpiride in healthy subjects.ABCB1 基因多态性对健康受试者左舒必利药代动力学的影响。
Neuroscience. 2010 Aug 11;169(1):378-87. doi: 10.1016/j.neuroscience.2010.04.065. Epub 2010 May 9.
3
The pharmacokinetics of paliperidone versus risperidone.帕利哌酮与利培酮的药代动力学比较。
Psychosomatics. 2010 Jan-Feb;51(1):80-8. doi: 10.1176/appi.psy.51.1.80.
4
Effects of CYP2D6 and CYP3A5 genotypes on the plasma concentrations of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients.CYP2D6和CYP3A5基因多态性对韩国精神分裂症患者血浆中利培酮及9-羟基利培酮浓度的影响。
J Clin Psychopharmacol. 2009 Jun;29(3):272-7. doi: 10.1097/JCP.0b013e3181a289e0.
5
Discovery of novel functional variants and extensive evaluation of CYP2D6 genetic polymorphisms in Koreans.韩国人中新的功能性变异的发现及CYP2D6基因多态性的广泛评估。
Drug Metab Dispos. 2009 Jul;37(7):1464-70. doi: 10.1124/dmd.108.022368. Epub 2009 Apr 13.
6
ABCB1 polymorphisms influence steady-state plasma levels of 9-hydroxyrisperidone and risperidone active moiety.ABCB1 多态性影响 9-羟基利培酮和利培酮活性代谢物的稳态血浆水平。
Ther Drug Monit. 2008 Oct;30(5):628-33. doi: 10.1097/FTD.0b013e3181858ca9.
7
Effects of CYP3A5 and MDR1 single nucleotide polymorphisms on drug interactions between tacrolimus and fluconazole in renal allograft recipients.CYP3A5和MDR1单核苷酸多态性对肾移植受者中他克莫司与氟康唑药物相互作用的影响。
Pharmacogenet Genomics. 2008 Oct;18(10):861-8. doi: 10.1097/FPC.0b013e328307c26e.
8
Functional polymorphism of the human multidrug resistance gene (MDR1) and polydipsia-hyponatremia in schizophrenia.人类多药耐药基因（MDR1）的功能多态性与精神分裂症中的烦渴性低钠血症
Neuromolecular Med. 2008;10(4):362-7. doi: 10.1007/s12017-008-8041-2. Epub 2008 Jun 10.
9
Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression.药物转运蛋白基因ABCB1的多态性可预测抑郁症的抗抑郁治疗反应。
Neuron. 2008 Jan 24;57(2):203-9. doi: 10.1016/j.neuron.2007.11.017.
10
Pharmacodynamic consequences of P-glycoprotein-dependent pharmacokinetics of risperidone and haloperidol in mice.利培酮和氟哌啶醇在小鼠体内P-糖蛋白依赖性药代动力学的药效学后果
Behav Brain Res. 2008 Apr 9;188(2):298-303. doi: 10.1016/j.bbr.2007.11.009. Epub 2007 Nov 21.
Zotero 插件