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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。

相似文献

1
[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].[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]
Gan To Kagaku Ryoho. 1991 Jul;18(8):1349-55.
2
[Pharmacological and clinical studies on lipiodol emulsion for hepatocellular carcinoma].
Gan To Kagaku Ryoho. 1988 Aug;15(8 Pt 2):2544-8.
3
[Preoperative chemoembolization of iopamiron-solved adriamycin and lipiodol on hepatocellular carcinoma--clinicopathological study of ten surgical cases].
Gan To Kagaku Ryoho. 1988 Aug;15(8 Pt 2):2549-56.
4
[Pharmacokinetics and targeting characteristics of adriamycin after canine hepatic arterial embolization with adriamycin-lipiodol emulsion].[阿霉素-碘油乳剂犬肝动脉栓塞术后阿霉素的药代动力学及靶向特性]
Di Yi Jun Yi Da Xue Xue Bao. 2004 Dec;24(12):1428-30.
5
[Behavior of anti-cancer drug of transcatheter hepatic segmental arterial chemoembolization using lipiodol mixed with an anti-cancer drug followed by gelatin sponge assessed by Tc-99m pertechnetate].[使用与抗癌药混合的碘油随后用明胶海绵进行经导管肝段动脉化疗栓塞的抗癌药行为,通过锝-99m高锝酸盐评估]
Gan To Kagaku Ryoho. 1990 Aug;17(8 Pt 2):1725-30.
6
[Oily chemoembolization of hepatoma].[肝癌的油性化疗栓塞术]
Gan To Kagaku Ryoho. 1987 Feb;14(2):381-7.
7
[Experimental studies on the dynamics of anticancer agents in transcatheter arterial chemo-embolization. Magnetic resonance imaging using emulsions containing lipiodol and Gd-DTPA].[经导管动脉化疗栓塞术中抗癌药物动力学的实验研究。使用含碘油和钆喷酸葡胺的乳剂进行磁共振成像]
Nihon Ika Daigaku Zasshi. 1991 Jun;58(3):285-95. doi: 10.1272/jnms1923.58.285.
8
Efficacy of emulsion containing Gd-DTPA and lipiodol in hepatic transcatheter arterial embolization.含钆喷酸葡胺与碘油的乳剂在肝动脉导管栓塞中的疗效
Radiat Med. 1993 Sep-Oct;11(5):187-90.
9
[Chemoembolization].
Gan To Kagaku Ryoho. 1987 May;14(5 Pt 2):1656-63.
10
[Accumulation of lipiodol in hepatocellular carcinoma after transarterial chemoembolization with 5 FU-lipiodol-emulsion].
Gan To Kagaku Ryoho. 1988 Aug;15(8 Pt 2):2557-61.

引用本文的文献

1
Effective Utilization of Conventional Transarterial Chemoembolization and Drug-eluting Bead Transarterial Chemoembolization in Hepatocellular Carcinoma: A Guide to Proper Usage.传统经动脉化疗栓塞术与载药微球经动脉化疗栓塞术在肝细胞癌中的有效应用:正确使用指南
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Development of pumping emulsification device with glass membrane to form ideal lipiodol emulsion in transarterial chemoembolization.研发具有玻璃膜的泵送乳化装置,以在经动脉化疗栓塞术中形成理想的碘化油乳剂。
Eur Radiol. 2018 May;28(5):2203-2207. doi: 10.1007/s00330-017-5197-x. Epub 2017 Dec 15.
3
Comparison of drug release and pharmacokinetics after transarterial chemoembolization using diverse lipiodol emulsions and drug-eluting beads.
使用不同的碘油乳剂和药物洗脱微球经动脉化疗栓塞术后的药物释放及药代动力学比较。
PLoS One. 2014 Dec 31;9(12):e115898. doi: 10.1371/journal.pone.0115898. eCollection 2014.
4
The current practice of transarterial chemoembolization for the treatment of hepatocellular carcinoma.经动脉化疗栓塞治疗肝细胞癌的当前实践。
Korean J Radiol. 2009 Sep-Oct;10(5):425-34. doi: 10.3348/kjr.2009.10.5.425. Epub 2009 Aug 25.