新型口服抗凝药的药物基因组学研究现状
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摘要
口服抗凝药是预防或治疗血栓栓塞性疾病的有效措施,相比于传统口服抗凝药华法林,新型口服抗凝药因具有抗凝效果相当,使用方便,且安全风险低等特点,近年来在临床上应用广泛,伴随临床使用及研究发现,新型口服抗凝药的抗凝治疗存在较大的个体差异。因此,本文对新型口服抗凝药的药理作用、药代动力学特征以及药物基因组学研究现状做一综述,以期为新型口服抗凝药的个体化治疗研究提供参考。
Oral anticoagulant is an effective measure to prevent or treat thromboembolic diseases. Compared with the traditional oral anticoagulant warfarin,the new oral anticoagulants have the characteristics of same anticoagulant effect,easy to use,and low safety risk,therefore have been widely used in clinical practice in recent years. With clinical use and research,there are large individual differences in anticoagulant therapy for new oral anticoagulants. We reviewed the pharmacological effects,pharmacokinetics and pharmacogenomics of new oral anticoagulants in order to provide reference for individualized treatment of new oral anticoagulants.
Oral anticoagulant is an effective measure to prevent or treat thromboembolic diseases. Compared with the traditional oral anticoagulant warfarin,the new oral anticoagulants have the characteristics of same anticoagulant effect,easy to use,and low safety risk,therefore have been widely used in clinical practice in recent years. With clinical use and research,there are large individual differences in anticoagulant therapy for new oral anticoagulants. We reviewed the pharmacological effects,pharmacokinetics and pharmacogenomics of new oral anticoagulants in order to provide reference for individualized treatment of new oral anticoagulants.
引文
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[17]VANDELL A G,WALLKER J,BROWNKS,et al. Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism[J]. Heart,2017,103(22):1800-1805.
[2]SYCHEV D A,LEVANOV A N,SHELEKHOVA T V,et al. The impact of ABCB1(rs1045642 and rs4148738)and CES1(rs2244613)genepolymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty[J/OL].Pharmgenomics Pers Med,2018,11:127-137. 2018-07-25[2019-01-04]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC6064159/.
[3]GOUIN-THIBAULT I,DELAVENNE X,BLANCHARD A,et al.Interindividual variability in dabigatran and rivaroxaban exposure:contribution of ABCB1 genetic polymorphisms and interaction with clarithromycin[J]. J Thromb Haemost,2017,15(2):273-283.
[4]PARE G,ERIKSSON N,LEHR T,et al. Genetic determinants of dabigatran plasma levels and their relation to bleeding[J]. Circulation,2013,127(13):1404–1412.
[5]ASIC A,MARJANOVIC D,MIRAT J,et al. Pharmacogenetics of novel oral anticoagulants:A review of identified gene variants&future perspectives[J]. Per Med,2018,15(3):209-221.
[6]SHI J,WANG X,NGUYEN J H,et al. Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E(rs71647871)and gender[J/OL]. Biochem Pharmacol,2016,119:76-84. 2016-11-01[2019-01-05]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5061634/.
[7]HARDER S. Pharmacokinetic and pharmacodynamic evaluation of rivaroxaban:considerations for the treatment of venous thromboembolism[J/OL]. Thromb J,2014,12:22. 2014-10-28[2019-01-05]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC4334601/.
[8]ING LORENZINI K,DAALI Y,FONTANA P,et al. Rivaroxabaninduced hemorrhage associated with ABCB1 genetic defect[J/OL].Front Pharmacol,2016,7:494. 2016-12-19[2019-01-05]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5165251/.
[9]SYCHEV D A,VARDANYAN A,ROZHKOV A,et al. CYP3A Activity and rivaroxaban serum concentrations in russian patients with deep vein thrombosis[J]. Genet Test Mol Biomarkers,2018,22(1):51-54.
[10]ASIC A,MARJANOVIC D,MIRAT J,et al. Pharmacogenetics of novel oral anticoagulants:a review of identified gene variants&future perspectives[J]. Per Med,2018,15(3):209-221.
[11]HURST K V,O'CALLAGHAN J M,HANDA A. Quick reference guide to apixaban[J/OL]. Vasc Health Risk Manag,2017,13:263-267. 2017-07-10[2019-01-05]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5513886/.
[12]DIMATTEO C,D'ANDREA G,VECCHIONE G,et al. ABCB1SNP rs4148738 modulation of apixaban interindividual variability[J]. Thromb Res,2016,145(1):24-26.
[13]KRYUKOV A V,SYCHEV D A,ANDREEV D A,et al. Influence of ABCB1 and CYP3A5 gene polymorphisms on pharmacokinetics of apixaban in patients with atrial fibrillation and acute stroke[J/OL].Pharmgenomics Pers Med,2018,11:43-49. 2018-03-22[2019-01-05]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5868588/.
[14]NAGAR S,WALTHER S,BLANCHARD R L. Sulfotransferase(SULT)1A1 polymorphic variants*1,*2,and*3 are associated with alteredenzymatic activity,cellular phenotype,and protein degradation[J]. Mol Pharmacol,2006,69(6):2084-2092.
[15]STACY Z A,CALL W B,HARTMANN A P,et al. Edoxaban:a comprehensive review of the pharmacology and clinical data for the management of atrial fibrillation and venous thromboembolism[J].Cardiol Ther,2016,5(1):1-18.
[16]VANDELL A G,LEE J,SHI M,et al. An integrated pharmacokinetic/pharmacogenomic analysis of ABCB1 and SLCO1B1 polymorphisms on edoxaban exposure[J]. Pharmacogenomics J,2018,18(1):153-159.
[17]VANDELL A G,WALLKER J,BROWNKS,et al. Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism[J]. Heart,2017,103(22):1800-1805.