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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >The stereoselective effects of bucolome on the pharmacokinetics and pharmacodynamics of racemic warfarin.
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The stereoselective effects of bucolome on the pharmacokinetics and pharmacodynamics of racemic warfarin.

机译：bucolome对消旋华法林药代动力学和药效学的立体选择性作用。

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摘要

The objective of this study was to investigate the stereoselective influence of bucolome on the pharmacokinetics and pharmacodynamics of warfarin in Japanese inpatients with heart disease. Thirty patients were administered a fixed-maintenance dose of warfarin alone once a day for at least 7 days. The other 25 patients were concomitantly administered warfarin and a 300 mg dose of bucolome once a day, and blood samples were collected on days 1, 4, 7, 14, or 21 after administration of bucolome. Serum concentration of warfarin enantiomers was measured by a chiral reversed-phase HPLC-ultraviolet detection method. The PT-INR was used as a measure of the pharmacodynamic effect of warfarin. Coadministration of bucolome and warfarin had no effect on serum (R)-warfarin concentration and significantly increased serum (S)-warfarin concentration compared with warfarin alone. The PT-INR of warfarin alone was significantly lower with bucolome cotreatment. These results indicate that the augmented anticoagulant effect of warfarin by bucolome is due to inhibition of (S)-warfarin metabolism in vivo. When bucolome is added to a stabilized regimen of warfarin therapy, the dose of warfarin should be reduced by about 30% to 60%, and caution should be exercised during the first 7 days after coadministration of bucolome.
机译：这项研究的目的是调查布考洛姆对日本心脏病患者华法林的药代动力学和药效学的立体选择性影响。 30名患者每天单独接受固定剂量的华法林至少7天。其余25例患者每天同时服用华法林和300 mg bucolome，并在服用bucolome后第1、4、7、14或21天收集血液样本。华法林对映异构体的血清浓度通过手性反相HPLC-紫外检测法测定。 PT-INR被用作华法林药效学作用的量度。与单独使用华法林相比，bucolome和华法林的共同给药对血清（R）-华法林浓度无影响，并且血清（S）-华法林浓度显着增加。 bucolome联合治疗单独使用华法林的PT-INR显着降低。这些结果表明，bucolome增强了华法林的抗凝作用是由于体内对（S）-华法林代谢的抑制。当华法林治疗的稳定方案中加入布科洛美时，应将华法林的剂量减少约30％至60％，并应在布科洛美合用后的前7天谨慎行事。

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