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利用药代动力学模型调整苯丙香豆素剂量。

Adjustment of phenprocoumon dosage utilizing a pharmacokinetic model.

作者信息

Böhm K, Vogel G, Barthel W

机构信息

Department of Internal Medicine, Medical Academy Erfurt, GDR.

出版信息

Folia Haematol Int Mag Klin Morphol Blutforsch. 1988;115(1-2):141-6.

PMID:2459009
Abstract

According to a pharmacokinetic model, the adjustment of a phenprocoumon (PPC) standard dosage based on experimentally determined means values of the parameters volume of distribution and biological half-life will yield in more than 50% of the individuals the desired plasma PPC concentration. In 25 patients it was tested, whether the thus derived loading and maintenance doses, 376.8 and 35.2 micrograms PPC per kg b. wt., resp., actually lead to the predicted optimum plasma PPC concentration of 2.0 micrograms/ml. After initiating dosage, the plasma PPC concentrations were determined over a time period of 30 days. As predicted by the model, in 72% of the patients the average steady-state plasma PPC concentrations were within the range of 1.7 and 2.3 micrograms/ml. The data obtained were used to newly calculate mean values of the volume of distribution, the biological half-life, and the total body clearance of PPC. The mean biological half-life of PPC derived was somewhat shorter than that used for the calculation of the standard dose. Quick-values were estimated concomitantly with the plasma PPC concentrations. They revealed an optimum anticoagulation (15-25%) in 96% of the patients.

摘要

根据药代动力学模型,基于实验测定的分布容积和生物半衰期参数的均值来调整苯丙香豆素(PPC)的标准剂量,在超过50%的个体中会产生所需的血浆PPC浓度。对25名患者进行了测试,以确定由此得出的负荷剂量和维持剂量,即每千克体重分别为376.8微克和35.2微克PPC,是否真的能导致预测的最佳血浆PPC浓度2.0微克/毫升。开始给药后,在30天的时间段内测定血浆PPC浓度。正如模型所预测的,72%的患者平均稳态血浆PPC浓度在1.7至2.3微克/毫升范围内。所获得的数据用于重新计算PPC的分布容积、生物半衰期和全身清除率的均值。得出的PPC平均生物半衰期比用于计算标准剂量的生物半衰期略短。与血浆PPC浓度同时估算快速值。结果显示,96%的患者具有最佳抗凝效果(15 - 25%)。

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