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目的 研究 32名心脏瓣膜置换患者口服华法林达稳态后 ,血浆中华法林两种对映体S 华法林 (S W)及R 华法林 (R W)与药效间的关系。方法 采用Quick法测定服药前及服药 5d后的凝血酶原时间 (PT) ,并以此计算凝血酶原复合物活性(PCA) ;柱前衍生化HPLC测定稳态时两种对映体浓度 ;研究S W ,R W对数浓度与PCA间的相关性。结果 32名患者服药前后PT分别为 (12 .83± 1.44 )和 (19.2 1± 3.47)s;稳态时S W与R W浓度分别为 (0 .2 9± 0 .2 1)和 (0 .6 0± 0 .37) μg·ml-1;PCA与ln(S Wp)和ln(R Wp)的相关系数分别为 0 .5 6和 0 .5 5 ;而PCA与剂量相关系数仅为 0 .2 7。结论 华法林对映体浓度与药效之间具有显著的相关性 ,提示华法林对映体血药浓度与剂量相比更能反映华法林的药效。
Objective To investigate the relationship between warfarin (S W) and R warfarin (R W) and the pharmacodynamics of warfarin in plasma of 32 cardiac valve replacement patients after oral administration of warfarin steady state. Methods The prothrombin time (PT) was measured by Quick method before and 5 days after administration. Prothrombin complex activity (PCA) was calculated by using Quick method. Pre enantiomeric derivatization (HPLC) was used to determine the two enantiomeric concentrations at steady state. Study of SW, RW logarithmic concentration and PCA correlation. Results The PT of 32 patients before and after treatment were (12.83 ± 1.44) and (19.2 1 ± 3.47) s, respectively. The steady-state SW and RW concentrations were (0.29 ± 0.21) and 0 ± 0.37) μg · ml-1; the correlation coefficients between PCA and ln (S Wp) and ln (R Wp) were 0.56 and 0.55, respectively; while the correlation coefficient between PCA and dose was only 0. 2 7. Conclusion There is a significant correlation between warfarin enantiomeric concentration and pharmacodynamics, suggesting that the warfarin enantiomer blood concentration is more dose-response than warfarin.