The effect of CYP2C19 genotypes on the pharmacokinetics of warfarin enantiomers
The effect of CYP2C19 genotypes on the pharmacokinetics of warfarin enantiomers
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CYP2C19基因型对华法林对映体药代动力学的影响
DOI：
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发表时间：
2008
影响因子：
2
通讯作者：
T. Tateishi
中科院分区：
文献类型：
--
作者：
T. Uno;K. Sugimoto;K. Sugawara;T. Tateishi
为了解华法林对映体与细胞色素P450 2C19(细胞色素P450 2C19)基因的相关性，研究了14名受试者，其中7名为纯合子广泛代谢者(HmEM)，7名为不良代谢者(PM)。单次口服10 mg的消旋华法林后，在120 h内测量了华法林对映体的血药浓度和凝血酶原时间(PT-INR)。所有受试者的平均血药浓度和消除半衰期都是S华法林的2倍。此外，PMS的血药浓度-时间曲线下面积(AUC0-∞)和(R)-华法林的消除半衰期显著大于HMEM(分别为P = 0.0 0 5和P = 0.0 101)。华法林对映体的AUC值：HMEM为0·51，PM为0·37(P = 0·0052)。而(S)-华法林在HMEM中的所有药动学参数与PM相比均无显著差异。用来衡量抗凝效果的PT-INR在HMEM和PM之间没有显著差异。这些结果表明，CYP2C19活性在(R)-华法林的药代动力学中起重要作用。然而，当华法林作为外消旋体给药时，这种差异在华法林的药效学中并没有转化为任何显著的效果。
The aim of this study was to elucidate the pharmacokinetics and pharmacodynamics of warfarin enantiomers in relation to cytochrome P450 2C19 (CYP2C19) genotypes.Fourteen subjects, of whom seven were homozygous extensive metabolizers (hmEMs) and seven were poor metabolizers (PMs) for CYP2C19, were enrolled. After a single oral 10 mg dose of racemic warfarin, the plasma concentrations of the warfarin enantiomers and prothrombin time expressed as international normalized ratio (PT‐INR) were measured over the course of 120 h.The mean plasma concentrations and elimination half‐life of (R)‐warfarin of all the subjects were about 2‐fold greater than those of (S)‐warfarin. Additionally, the area under the plasma concentration–time curve from zero to infinity (AUC0–∞) and the elimination half‐life of (R)‐warfarin in PMs were significantly greater than those in hmEMs (P = 0·0005 and P = 0·0101 respectively). The S/R ratios of AUC of warfarin enantiomers were 0·51 in hmEMs and 0·37 in PMs (P = 0·0052). Whereas no difference was found in all pharmacokinetic parameters of (S)‐warfarin in hmEMs compared with PMs. No significant difference in PT‐INR, used as a measure of anticoagulant effect, was found between the hmEMs and PMs.These results show that CYP2C19 activity is important in the pharmacokinetics of (R)‐warfarin. However, when warfarin is administered as a racemate, this difference is not translated into any significant effect in the pharmacodynamics of warfarin.
影响因子：
3.6
作者：
S. M. Morais;G. Wilkinson;J. Blaisdell;U. Meyer;K. Nakamura;J. Goldstein
通讯作者：
S. M. Morais;G. Wilkinson;J. Blaisdell;U. Meyer;K. Nakamura;J. Goldstein
影响因子：
158.5
作者：
Rieder, MJ;Reiner, AP;Rettie, AE
通讯作者：
Rettie, AE