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首页> 外文OA文献 >Utjecaj kombinacije polimorfizma gena CYP2C9, VKORC1 i MDR1 na individualizaciju terapije varfarinom Influence of combination of CYP2C9, VKORC1 and MDR1 geneudpolymorphisms on individualization of warfarine therapy
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Utjecaj kombinacije polimorfizma gena CYP2C9, VKORC1 i MDR1 na individualizaciju terapije varfarinom Influence of combination of CYP2C9, VKORC1 and MDR1 geneudpolymorphisms on individualization of warfarine therapy

机译：CYp2C9，VKORC1和mDR1基因多态性对华法林治疗个体化的影响CYp2C9，VKORC1和mDR1基因组合的影响华法治疗个体化的多态性

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摘要

Despite that warfarine has been used as an anticoagulant for many years it's dosing presents audchallenging task owing to its narrow therapeutic range and large variability in dose-responseudrelationship. Warfarine therapy usually started after assessment of clinical characteristicsud(age, body size, race), vitamin K intake and use of concomitant medications. Inappropriateuddosing continues to contribute to significant morbidity and mortality due to thromboticuddisease and bleeding complications.udGenetic variations in the cytochrome P450 polypeptide 9 (CYP2C9) and vitamin K epoxideudreductase (VKORC1) have been identified as the most important enzymes in the warfarinudpharmacological pathway. Observational studies have indicated CYP2C9, VKORC1 andudMDR1 potential effect but randomized clinical trials resulted in contradictory findings.udThe aim of this study is to evaluate the influence of combination of CYP2C9, VKORC1 andudMDR1 gene polymorphisms on individualization of warfarine therapy. We have not foundudstatistically significant benefits from genotype guided dosing in deep-vein thrombosis andudpulmonary embolism, but in atrial fibrillation percentage of time with INR therapeutic rangeudwas statistically significantly longer in this, than in clinically guided dosing group. Stableuddose was achieved by statistically significantly larger number of patients whose dose hadudbeen determined by genotype and clinical characteristics than in clinically-only-guided dosingudgroup.
机译：尽管华法林已被用作抗凝剂多年，但由于其治疗范围狭窄且剂量反应/非相关性差异较大，其给药剂量仍具有挑战性。通常在评估临床特征，年龄，体重，种族，维生素K摄入量和使用伴随药物后开始进行华法林治疗。由于血栓形成 uddisease和出血并发症，不适当的过量剂量继续导致明显的发病率和死亡率。 ud细胞色素P450多肽9（CYP2C9）和维生素K环氧 udreductase（VKORC1）的遗传变异已被确定为该酶中最重要的酶。华法林 ud药理学途径。观察性研究表明CYP2C9，VKORC1和 udMDR1的潜在作用，但随机临床试验导致矛盾的发现。我们没有发现基因型指导剂量在深静脉血栓形成和肺栓塞中具有统计学上的显着优势，但是与临床指导给药组相比，INR治疗范围内的心房颤动时间百分比在统计学上显着更长。通过统计学上显着更多的患者剂量（由基因型和临床特征决定）的剂量比仅由临床指导的剂量/ udgroup达到的患者稳定/过量。

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    Makar-Aušperger Ksenija;

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