Several‐fold increase in risk of overanticoagulation by CYP2C9 mutations

摘要: Objective Our objective was to prospectively study the impact of CYP2C9 polymorphism (*2 and *3) on risk overanticoagulation during induction phase warfarin therapy. Methods Blood samples for genotyping were collected from 219 patients requiring therapy, clinical data first 3 weeks medication. Patients divided into groups according genotype, as follows: *1 (homozygous), *2 (*1/*2 *2/*2), *3 (any genotype containing allele). Results During week treatment, relative achieving at least 1 international normalized ratio (INR) value above therapeutic interval (2–3) 2.8 (95% confidence interval, 1.2–6.7) 6.1 (2.7–13.6) in groups, respectively (with used control). During second week, corresponding values 2.1 (1.2–3.7) 3.5 (2.1–5.8), respectively. By third genetic no longer evident, presumably a result successful dose individualization. Increased INR levels (compared with group) already demonstrated group fourth treatment day. Conclusions The CYP2C9*2 single-nucleotide polymorphisms significantly increase 2 increased evident after only 4 days' carriers. Our prospective are consistent results previous retrospective studies indicate that may be means improving safety induction. Clinical Pharmacology & Therapeutics (2005) 78, 540–550; doi: 10.1016/j.clpt.2005.08.006