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Pharmacokinetic interaction with digoxin and glucocorticoids in rats detected by radio-immunoassay using a novel specific antiserum.

机译:通过使用新型特异性抗血清的放射免疫分析法检测到的大鼠中与地高辛和糖皮质激素的药代动力学相互作用。

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We previously prepared a more specific antiserum (Antiserum-I) to digoxin (Dx) compared with commercially available anti-Dx antiserum (Antiserum-II), clinically used in the therapeutic drug monitoring of Dx. The aims of this study are to compare Dx disposition kinetics by radio-immunoassay (RIA) using Antiserum-I and Antiserum-II, and evaluate the drug-drug interaction with Dx and glucocorticoids in rats. When Dx metabolites were added to rat serum containing Dx, the recovery ratios using Antiserum-I showed 100 to 110% and were remarkably lower than those using Antiserum-II. In rats, serum concentration-time courses of Dx after a single i.v. or p.o. administration of Dx (0.017 mg/kg) by RIA using Antiserum-I were much lower than those using Antiserum-II. The area under the concentration-time course of Dx was significantly lower than that using Antiserum-II and the total body clearance values were significantly higher, while an obvious change of bioavailability was not observed. When using Antiserum-I, rats twice and six times pretreated with dexamethasone (75 mg/kg/day, i.p.) and prednisolone (69 mg/kg/day, i.p.), respectively, showed significant change of the pharmacokinetic parameters of Dx compared with the control rats. In contrast, using Antiserum-II, it took three and nine times of pretreatment with dexamethasone and prednisolone, respectively, to significantly change the parameters of Dx. In conclusion, these results demonstrate that Antiserum-I is very useful not only to more precisely monitor serum Dx levels, but also to determine earlier the drug-drug interaction with glucocorticoids than Antiserum-II.
机译:与临床上用于Dx的治疗性药物监测的市售抗Dx抗血清(Antiserum-II)相比,我们以前制备了对地高辛(Dx)更特异性的抗血清(Antiserum-I)。本研究的目的是通过使用抗血清I和抗血清II的放射免疫分析(RIA)比较Dx的处置动力学,并评估与Dx和糖皮质激素在大鼠中的药物相互作用。当将Dx代谢物添加到含有Dx的大鼠血清中时,使用Antiserum-I的回收率显示为100%至110%,并且显着低于使用Antiserum-II的回收率。在大鼠中,单次静脉注射后Dx的血清浓度-时间进程。或p.o.通过RIA使用Antiserum-I施用Dx(0.017 mg / kg)的剂量远低于使用Antiserum-II的剂量。 Dx的浓度-时间过程下的面积显着低于使用Antiserum-II的面积,并且总体清除率值显着更高,而未观察到生物利用度的明显变化。当使用Antiserum-I时,分别用地塞米松(75 mg / kg /天,腹膜内)和泼尼松龙(69 mg / kg /天,腹膜内)预处理的大鼠两次和六次显示Dx的药代动力学参数与对照大鼠。相反,使用Antiserum-II,分别用地塞米松和泼尼松龙进行预处理的时间分别为三倍和九倍,从而显着改变了Dx的参数。总之,这些结果表明,Antiserum-I不仅在更精确地监测血清Dx水平方面非常有用,而且比Antiserum-II更早地确定药物与糖皮质激素的相互作用。

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