Combination index of the concentration and in vivo antagonism activity of racemic warfarin and its metabolites to assess individual drug responses
Combination index of the concentration and in vivo antagonism activity of racemic warfarin and its metabolites to assess individual drug responses
复制标题
外消旋华法林及其代谢物的浓度和体内拮抗活性的组合指数评估个体药物反应
DOI：
10.1007/s11239-018-1780-5
复制
发表时间：
2018
影响因子：
4
通讯作者：
Ohyama Kaname
中科院分区：
文献类型：
--
作者：
Kobayashi Shuhei;Ishii Koji;Yamada Yasuko;Ryu Emi;Hashizume Junya;Nose Seiichi;Hara Tetsuya;Nakashima Mikiro;Ohyama Kaname
本研究旨在研究体内维生素K环氧化物还原酶复合物1（VKOR）的“实际”拮抗活性（通过R-和S-华法林对映体及其代谢物的浓度和报告的抗凝活性计算）是否与华法林的每周剂量相关。本研究选取五位接受姑息治疗的病患，并以高效液相色谱-紫外检测法分析20份血清样本。S-华法林、R-华法林、7-和10-羟基华法林的体内VKOR抑制活性计算为药物或代谢物浓度与IC 50的比值。S-和R-华法林、7-羟基华法林和10-羟基华法林的平均药物浓度（± SD）分别为334 ± 154 ng/ml、370 ± 115 ng/ml、42 ± 15 ng/ml和80 ± 44 ng/ml。然后计算S-和R-华法林、7-羟基华法林和10-羟基华法林的体内VKOR实际拮抗活性。华法林周剂量与INR/实际拮抗活性比值之间具有良好的相关性（R2= 0.69-0.72），而华法林周剂量与INR（R2= 0.32）或活性（R2= 0.17-0.21）之间的相关性较差。实际拮抗活性沿着INR与华法林剂量相关性良好。该参数可能有助于预测或改变华法林剂量，但需要在更大规模的研究中进一步验证。
The present study was undertaken to examine whether in vivo vitamin K epoxide reductase complex 1 (VKOR) “actual” antagonism activity, calculated by the concentrations and the reported anticoagulant activities of theR- andS-warfarin enantiomers and their metabolites, correlates with the weekly dose of warfarin. Five patients under palliative care were enrolled in our study and 20 serum samples were analyzed by an enantioselective high-performance liquid chromatography–ultraviolet detection method. In vivo VKOR inhibition activities ofS-warfarin,R-warfarin, 7- and 10-hydroxywarfarin were calculated as the ratio of drug or metabolite concentration to the IC50. The mean drug concentrations (± SD) ofS- andR-warfarin, 7-hydroxywarfarin and 10-hydroxywarfarin were 334 ± 154 ng/ml, 370 ± 115 ng/ml, 42 ± 15 ng/ml and 80 ± 44 ng/ml, respectively. Then, in vivo VKOR actual antagonism activities ofS- andR-warfarin, 7-hydroxywarfarin and 10-hydroxywarfarin were calculated. Good correlation (R2= 0.69–0.72) was obtained between the weekly warfarin dose and the ratios of INR/actual antagonism activity, while poor correlation was observed between the weekly warfarin dose and INR (R2= 0.32) or the activities (R2= 0.17–0.21). Actual antagonism activities along with the INR correlated well with the warfarin dose. This parameter may be useful for predicting or altering warfarin doses, although further verification in a larger study is required.
登录
查看更多内容
DOI：
10.1056/nejmoa1310669
发表时间：
2013-12-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kimmel SE;French B;Kasner SE;Johnson JA;Anderson JL;Gage BF;Rosenberg YD;Eby CS;Madigan RA;McBane RB;Abdel-Rahman SZ;Stevens SM;Yale S;Mohler ER 3rd;Fang MC;Shah V;Horenstein RB;Limdi NA;Muldowney JA 3rd;Gujral J;Delafontaine P;Desnick RJ;Ortel TL;Billett HH;Pendleton RC;Geller NL;Halperin JL;Goldhaber SZ;Caldwell MD;Califf RM;Ellenberg JH;COAG Investigators
通讯作者：
COAG Investigators
影响因子：
7.5
作者：
Odén, A;Fahlén, M;Hart, RG
通讯作者：
Hart, RG
研究华法林和羟基华法林异构体反相解析的二维高效液相色谱方法。
DOI：
10.1016/j.chroma.2014.08.025
发表时间：
2014
期刊：
Journal of chromatography. A
影响因子：
--
作者：
E. Regalado;J. Schariter;C. Welch
通讯作者：
C. Welch
影响因子：
5.8
作者：
Yamazaki, H;Shimada, T
通讯作者：
Shimada, T
影响因子：
2.6
作者：
Takahashi, Harumi;Wilkinson, Grant R.;Echizen, Hirotoshi
通讯作者：
Echizen, Hirotoshi