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[紫杉醇在实验动物中的药代动力学。第2部分。组织分布]

[Pharmacokinetics of paclitaxel in experimental animals. Part 2. Tissue distribution].

作者信息

Fujita H, Okamoto M, Takao A, Mase H, Kojima H

机构信息

Dept. of Bacteriology, School of Dental Medicine, Tsurumi University.

出版信息

Gan To Kagaku Ryoho. 1994 Apr;21(5):659-64.

PMID:7908792
Abstract

In S 180 bearing male mice, paclitaxel was rapidly distributed to various tissues within 10 minutes. The highest AUC was seen in the liver, and relatively high in the pancreas, kidney, thymus, intestine, stomach and lung. The concentration of paclitaxel in tumor tissue was not so high early time after administration, but was sustained for a long time with a half life of 12.3 hr. Elimination from the testis and thymus was also slow. The drug level in the brain was very low. In M 109 bearing female CDF1 mice, the distribution and elimination profile of paclitaxel was comparable to that in S 180 mice. The concentration of paclitaxel in the ovary, lung and uterus decreased slowly. In M 109 tumor, which was very sensitive to paclitaxel, the drug had a higher and long lasting distribution compared with S 180 tumor. In S 180 tumor bearing mice pretreated with CCl4, the paclitaxel level was found to be lower in the liver and higher in the other tissues including tumor, plasma, urine and bile than in non-treated mice.

摘要

在接种S 180肿瘤的雄性小鼠中,紫杉醇在10分钟内迅速分布到各个组织。肝脏中的AUC最高,胰腺、肾脏、胸腺、肠道、胃和肺中的AUC相对较高。给药后早期肿瘤组织中紫杉醇的浓度不高,但能长时间维持,半衰期为12.3小时。从睾丸和胸腺的消除也很缓慢。脑中的药物水平非常低。在接种M 109肿瘤的雌性CDF1小鼠中,紫杉醇的分布和消除情况与S 180小鼠相当。卵巢、肺和子宫中紫杉醇的浓度缓慢下降。在对紫杉醇非常敏感的M 109肿瘤中,与S 180肿瘤相比,药物分布更高且持续时间更长。在经四氯化碳预处理的接种S 180肿瘤的小鼠中,发现肝脏中的紫杉醇水平低于未处理的小鼠,而在包括肿瘤、血浆、尿液和胆汁在内的其他组织中则高于未处理的小鼠。

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