Dosing algorithms for warfarin individualized therapy

Abstract

Abstract: Warfarin is the most usually used oral anticoagulant with narrow therapeutic window,wide inter-individual variability and high risks of bleeding or thromboembolism.How to accurately adjust the dosage of warfarin has been the key point and hot topic of the anticoagulant therapy.Many factors may influence the dosage of warfarin, especially genomic aspects(mainly CYP2C9,VKORC1 and CYP4F2). Over the last decade, there exist a new opportunity for warfarin individual treatment with the fast development of warfarin pharmacogenetic algorithms and Population Phamacoketic/Pharmacodynamic models.Based on numerous warfarin stable dosage prediction algorithms studies,this review updates the studies of warfarin personalized treatment,with the aim of providing evidence for clinical practice.

Key words: warfarin, personalized treatment, pharmacogenetic, dose algorithm, population pharmacokinetics pharmacodynamics

CLC Number:

R968

HU Jing, ZHU Junrong, YU Feng. Dosing algorithms for warfarin individualized therapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(5): 591-596.

References

[1] Oake N, Jennings A, Forster AJ,et al. Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy:a systematic review and meta-analysis[J]. CMAJ,2008,179(3):235-244.
[2] 张婷,胡永芳.华法林药物基因组学研究及临床应用进展[J].中国新药杂志,2008,17(8):630-634.
[3] Sanderson S,Emery J,Higgins J.CYP2C9 gene vailants,drug dose,and bleeding risk in warfarin-treated patients:a HuGEnet systematic review and meta-analysis [J].Genet Med,2005,7(2):97-104.
[4] Reitsma PH,vander Heijden JF,Groot AP,et al.A CI I 73T dimorphism in the VKORC1 gene determines eoumarin sensitivity and bleeding risk[J].PLoS Med,2005,2(10):312.
[5] Caldwell MD, Awad T, Johnson JA, et al. CYP4F2 genetic variant alters required warfarin dose [J]. Blood,2008,111(8):4106-4112.
[6] Borgiani P, Ciccacci C, Forte V, et al. CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population [J]. Pharmacogenomics, 2009,10(2): 261-266.
[7] Wei M, Ye F, Xie D,et al.A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and VKORC1 and clinical variables: Derivation in Han Chinese patients with non valvular atrial fibrillation [J].Thromb Haemost, 2012,107(6): 1083-1091.
[8] Ageno W, Johnson J, Nowacki B,et al. A computer generated induction system for hospitalized patients starting on oral anticoagulant therapy[J].Thromb Haemost,2000, 83(6):849-852.
[9] Caraco Y, Blotnick S,Muszkat M. CYP2C9 Genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study[J]. Clin Pharmacol Ther, 2008,83(3):460-470.
[10] Zhu Y,Shennan M,Reynolds KK,et al.Estimation of warfarin maintenance dose based on VKORC1 (-1639 G＞A) and CYP2C9 genotypes[J].Clin Chem,2007,53(7) : 1199-1205.
[11] Gage BF, Eby C,Johnson JA,et al.Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin[J].Clin Pharmacol Ther,2008,84(3) : 326-331.
[12] Klein TE,Altman RB,Eriksson N,et al.Estimation of the warfarin dose with clinical and pharmacogenetic data[J].N Engl J Med,2009,360(8) : 753-764.
[13] 都丽萍,梅丹,刘昌伟,等.CYP2C9及VKORCl基因多态性对华法林剂量和抗凝效果的影响[J].中国药学杂志,20l0,45(21):1628-1633.
[14] 谢爽.VKORCl与CYP2C9基因多态性对中国人口服华法林起始抗凝效果影响的研究[D].北京,中国协和医科大学学位论文.2009.
[15] Anderson JL,Home BD,Stevens SM,et al.Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation[J].Circulation,2007,116(22):2563-2570.
[16] 黄盛文,向道康,安邦权,等.华法林稳定剂量预测算法的临床应用[J].中华医学杂志,2011,91(48):3421-3425.
[17] 薛领,沈振亚,马心超,等. 基于CYP2C9和VKORCI的基因多态性华法林抗凝剂量模型的临床验证[C]. 2010年第五次中美医院药学服务高级论坛论文集.2010.
[18] Hillman MA, Wilke RA, Yale SH, et al. A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data[J]. Clin Med Res,2005,3(3): 137-145.
[19] 谭胜兰,彭娟,周新民,等.验证并比较华法林稳定剂量预测模型对中国心脏瓣膜置换术后患者预测准确性[J].中国临床药理学与治疗学,2012,17(9):1026-1033.
[20] 张晶,林美钦,邱罕凡,等. 基于药物基因组学的5种华法林给药模型的验证[C]. 2013年中国临床药学学术年会暨第九届临床药师论坛论文集.2013.
[21] 余靓平,宋洪涛,曾志勇,等.基于药物基因组学的华法林给药模型的验证[J].中华心血管病杂志,2012,40(7):614-619.
[22] Wen MS,Lee MTM,Chen JJ,et al.Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes[J].Clin pharmacol Ther,2008,84(1):83-89.
[23] 芮建中,张震.群体药代动力学/群体药效动力学原理及研究方法[J].医学研究生学报,2005,18(3):246-249.
[24] Scordo MG, Pengo V, Spinda E, et al. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance[J]. Clin Pharmacol Ther,2002,72(6):702-710.
[25] Takahashi H, Echizen H. Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin[J]. Pharmacogenomics J,2003, 3(4):202-214 .
[26] Lane S, Al-Zubiedi S, Hatch E,et al. The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors[J]. Brit J Clin Pharmaco,2011,73(1):66-76.
[27] Hamberg AK, Friberg LE, Hanséus K, et al. Warfarin dose prediction in children using pharmacometric bridging-comparison with published pharmacogenetic dosing algorithms[J]. Eur J Clin Pharmacol,2013,69(6):1275-1283.
[28] Hamberg AK, Dahl ML, Barban M,et al. A PK-PD Model for Predicting the Impact of Age, CYP2C9, and VKORC1 Genotype on Individualization of Warfarin Therapy[J]. Clin Pharmacol Ther,2007,:81(4):529-538.
[29] Mc Donald MG, Rieder MJ, Nakano M, et al. CYP4F2 is a vitamin K1 oxidase: An explanation for altered warfarin dose in carriers of the V433M variant [J]. Mol Pharmacol, 2009,75(6):1337-1346.
[30] Derendorf H,Meibohm B.Modeling of pharmacokinetic/pharmacodynamic(PK/PD) relationships:concepts and perspectives[J].Phar Res,1999,16(2):176-185.
[31] Perez-Urizar J,Granados-Soto V,Flores-Murrieta FJ,et al. Pharmacokinetic-Pharmacodynamic modeling:why[J]. Arch Med Res,2000,31(6):539-545.
[32] Levy G,Mager DE,Cheung WK,et al. Comparative pharmacokinetic of coumarin anticoagulants L:Physiologic modeling of S-warfarin in rats and pharmacologic target-mediated warfarin disposition in man[J].J Pharm Sci,2003,92(5):985-994.
[33] Tomohiro S, Hiroko T. Warfarin-dosing algorithm based on a Population pharmacokinetic/pharmacodynamic model combined with forecasting[J].Pharmacogenomics,2009,10(8):1257-1266.