华法林在心脏瓣膜置换患者中对映体药效学研究

Pharmacodynamics of warfarin enantiomers in patients with cardiac valve replacement

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 study the correlation between the steady state plasma concentrations of warfarin enantiomers and its pharmacodynamics in 32 patients with cardiac valve replacement after oral administration of recemic warfarin.METHODS Prothrombin times (PT) were measured by quicks method before and after warfarin were given for 5 days and the prothrombin complex activity (PCA) was calculated thereafter.The plasma concentrations of S warfarin (S W) and R warfarin(R W) were determined by HPLC with a precolumn derivatization.The correlation was studied between the plasma concentration of warfarin enantiomers and PCA.RESULTS The PT before and after warfarin was given for 5 days were (12.83±1.44) and (19.21±3.47) s,respectively.The plasma concentrations of S W and R W were (0.29± 0.21 ) and (0.60±0.37) μg·ml -1 ,respectively.The correlation coefficients between PCA and ln(S W p),PCA and ln(R W p) were 0.56 and 0.55( P <0.05),respectively.However,the correlation coefficients between PCA and dose was only 0.27.CONCLUSION It seems that there are significant correlations between concentrations of warfarin enantiomers and its pharmacodynamics.Therefore,the concentrations of warfarin enantiomers is a better index of its effecacy than its dose.