11-脱氧米索前列醇灌胃后药动学性质的研究

R. M. Kataeva, E. F. Agletdinov, K. V. Bulygin, V. Kataev, N. Ivanova, S. F. Gabdrakhmanova, T. Sapozhnikova
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引用次数: 1

摘要

目的:建立11-脱氧咪异前列醇灌胃后的主要药动学参数。材料和方法。实验以410只体重180 ~ 220 g的雌性纯白大鼠为实验对象,按2.0 mg/kg的剂量灌胃11-脱氧肌醇。给药后12小时,分别于6、12、15、30分钟和每小时采血和器官检查。在这些时间间隔之后,测定实验动物血液和组织匀浆中的药物浓度,以及白天每小时尿液中的药物浓度。采用液相色谱仪(日本岛津LC-20 PROMI- NENCE,二极管阵列检测器SPD-20A)进行色谱分离。11-脱氧咪异前列醇可迅速从胃肠道吸收。该化合物在灌胃后15分钟达到血浆中最高浓度(6.625 μg/ml)。当这种情况发生时,代谢物- 11-脱氧异prostolic酸的浓度同时增加。11-脱氧异前列醇给药30分钟后,血浆中代谢物的最大浓度达到23.547µg/ml。11-脱氧咪异前列醇广泛分布于各个器官和组织中,对肌层和肝脏的亲和力最高。在肺、大脑和大网膜中发现了最少量的测试物质。11-脱氧咪异前列醇的活性代谢物集中分布于各脏器和组织中,以肌层和肝、肾中含量最多。在肺、大脑和大网膜中发现了最少量的测试物质。在研究的第一天测定尿中11-脱氧异前列腺酸,给药后6-8小时最大清除率。11-脱氧咪异前列醇灌胃后半衰期短(T1/2=0,550 h),这表明其不具有累积特性。药代动力学曲线的性质是单指数曲线。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
THE STUDY OF THE PHARMACOKINETIC PROPERTIES OF 11-DEOXYMISOPROSTOL AFTER INTRAGASTRIC ADMINISTRATION
The aim - to establish the main pharmacokinetic parameters of 11-deoxyimisoprostol after intragastric administration. Materials and methods. The experiments were performed on 410 white outbred rats - females weighing 180-220 g. 11-deoxymysoprostol was administered to rats intragastrally at a dose of 2.0 mg/kg. Blood and organs were taken for examination at 6, 12, 15, 30 minutes and hourly for 12 hours after administration. After these intervals, the concentration of the drug in the blood and tissue homogenates of laboratory animals was determined, and in the urine - every hour during the day. Chromatographic separation was carried out using a liquid chromatograph (Shimadzu, Japan LC-20 PROMI- NENCE with a diode - array detector SPD-20A).Results. 11-deoxyimisoprostol is rapidly absorbed from the gastrointestinal tract. The maximum (6.625 μg/ml) of the compound in the blood plasma is reached 15 minutes after intragastric administration. When this occurs, a simultaneous in - crease in the concentration of the metabolite - 11-deoxyimisoprostolic acid. The maximum concentration (23.547 µg/ml) of the metabolite in the blood plasma is reached 30 minutes after the administration of 11-deoxyimisoprostol. 11-deoxyimisoprostol is intensively distributed throughout the organs and tissues, while the compound has the highest affinity for myometrium and liver. The smallest quantities of the test substance were found in the lungs, the brain, and the omentum. The active metabolite of 11-deoxyimisoprostol is intensively distributed in organs and tissues, while in the greatest amounts it was detected in the myometrium and the liver and kidneys. The smallest quantities of the test substance were found in the lungs, the brain, and the omentum. In the urine, 11-deoxyimisoprostolic acid is determined during the first days of the study, with a maximum clearance of 6-8 hours after administration.Conclusion. 11-deoxyimisoprostol has a short half - life after intragastric administration (T1/2=0,550 h), which indicates the absence of cumulative properties. The nature of the pharmacokinetic curve is monoexponential.
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