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[阿霉素与碘油混合乳剂的药代动力学研究——组成和制备方法导致的差异以及大鼠肠系膜动脉注射后的行为]

[Pharmacokinetic study of adriamycin in the emulsion mixed with lipiodol-difference resulting from composition and methods of preparation, and behavior after mesenteric arterial injection in rat].

作者信息

Sakaguchi H, Uchida H, Nishimura Y, Guo Q Y, Yoshimura H, Ohishi H

机构信息

Dept. of Radiology and Oncoradiology, Nara Medical University, Kashihara, Japan.

出版信息

Gan To Kagaku Ryoho. 1991 Jul;18(8):1349-55.

PMID:1648890
Abstract

We experimentally investigated the pharmacokinetics of adriamycin (ADM) in a similar of transcatheter arterial chemoembolization therapy (TAE) of hepatocellular carcinoma using emulsion of lipiodol (Lp) mixed with ADM followed by gelatin sponge, and the difference resulting from composition and method of preparation of the emulsion as well as behavior after mesenteric arterial injection in rat. In in vitro study, the emulsion with iopamidol (iopamiron 300 : IP) was more stable than with amidotrizoic acid (60% Urografin : UG). The highest stability was found in the mixing ratio of Lp. IP and distilled water at 1 : 0.42 : 0.08. Frequent pumping also made the emulsion more stable. But in optimally composed emulsion, pumping 20 or 50 times made no difference in the stability during 30 min. which may be longer than the time from preparation to injection time of the emulsion in clinical application. After injection of the emulsion into the mesenteric artery which may simulate injection into the hepatic artery in hepatocellular carcinoma, the arterial blood flow was suspended. In the peripheral arteries the emulsion separated into two phases of Lp and ADM solution, forming striped pattern, and Lp embolization of the peripheral artery persisted for over 45 min. while ADM extravasated. These findings suggest that after Lp-TAE, Lp maintains an embolizing effect while ADM penetrates into the surrounding tumor tissue, and that this is an underlying mechanism for the anti-cancer effect of Lp-TAE.

摘要

我们通过实验研究了阿霉素(ADM)在类似于肝细胞癌经导管动脉化疗栓塞治疗(TAE)中的药代动力学,方法是使用与ADM混合的碘油(Lp)乳剂,随后注入明胶海绵,并研究了乳剂组成和制备方法的差异以及大鼠肠系膜动脉注射后的行为。在体外研究中,含碘帕醇(碘必乐300:IP)的乳剂比含泛影酸(60%泛影葡胺:UG)的乳剂更稳定。在Lp、IP和蒸馏水的混合比例为1:0.42:0.08时,稳定性最高。频繁抽吸也使乳剂更稳定。但在最佳组成的乳剂中,抽吸20次或50次在30分钟内对稳定性没有影响,这可能比临床应用中乳剂从制备到注射的时间更长。将乳剂注入肠系膜动脉(可模拟肝细胞癌肝动脉注射)后,动脉血流停止。在外周动脉中,乳剂分离为Lp和ADM溶液两个相,形成条纹状图案,外周动脉的Lp栓塞持续超过45分钟,而ADM渗出。这些发现表明,Lp-TAE后,Lp保持栓塞作用,而ADM渗透到周围肿瘤组织中,这是Lp-TAE抗癌作用的潜在机制。

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