通过乳糜微粒阻断了解淋巴给药:回顾性和前瞻性分析。

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Journal of pharmacological and toxicological methods Pub Date : 2024-08-02 DOI:10.1016/j.vascn.2024.107548
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引用次数: 0

摘要

科学家们开发并使用了各种模型来研究肠道淋巴吸收。其中一种方法是使用特定的阻断剂来影响乳糜微粒介导的药物淋巴吸收。目前使用的模型包括pluronic L-81、嘌呤霉素、长春花生物碱、秋水仙碱和环己亚胺。本综述对所使用的各种模型进行了深入分析,在评估现有报告的同时,还指出了当前研究中存在的不足。它还通过所讨论的模型探讨了肠道淋巴摄取途径及其阻断的药代动力学相关方面。Pluronic L-81 具有可逆效应、最小毒性和独特的作用模式。然而,它缺乏有关乳糜微粒途径阻断的临床报告,这可能是由于使用的浓度较低。嘌呤霉素和长春花生物碱虽然有毒性记录,但缺乏应用于药物肠道淋巴吸收的信息。其他长春花生物碱在影响甘油三酯谱方面显示出前景,可作为阻断剂进行测试。广泛用于药物开发的秋水仙碱和环己亚胺已证明具有疗效,环己亚胺因毒性较低而更受青睐。不过,还需要进一步研究秋水仙碱在人体中的有效剂量和毒性剂量,以了解其临床影响。此外,该综述还跟踪了口服淋巴靶向药物从摄入到排泄的完整过程,提供了考虑肠道淋巴途径的药代动力学方程,用于评估生物利用度。此外,还说明了尿液数据作为测量药物通过肠道淋巴管吸收的非侵入性方法的可能应用,并强调了在人体中使用特定阻断剂时发生药物相互作用的可能性。
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Understanding lymphatic drug delivery through chylomicron blockade: A retrospective and prospective analysis

Scientists have developed and employed various models to investigate intestinal lymphatic uptake. One approach involves using specific blocking agents to influence the chylomicron-mediated lymphatic absorption of drugs. Currently utilized models include pluronic L-81, puromycin, vinca alkaloids, colchicine, and cycloheximide. This review offers a thorough analysis of the diverse models utilized, evaluating existing reports while delineating the gaps in current research. It also explores pharmacokinetic related aspects of intestinal lymphatic uptake pathway and its blockage through the discussed models. Pluronic L-81 has a reversible effect, minimal toxicity, and unique mode of action. Yet, it lacks clinical reports on chylomicron pathway blockage, likely due to low concentrations used. Puromycin and vinca alkaloids, though documented for toxicity, lack information on their application in drug intestinal lymphatic uptake. Other vinca alkaloids show promise in affecting triglyceride profiles and represent possible agents to test as blockers. Colchicine and cycloheximide, widely used in pharmaceutical development, have demonstrated efficacy, with cycloheximide preferred for lower toxicity. However, further investigation into effective and toxic doses of colchicine in humans is needed to understand its clinical impact. The review additionally followed the complete journey of oral lymphatic targeting drugs from intake to excretion, provided a pharmacokinetic equation considering the intestinal lymphatic pathway for assessing bioavailability. Moreover, the possible application of urinary data as a non-invasive way to measure the uptake of drugs through intestinal lymphatics was illustrated, and the likelihood of drug interactions when specific blockers are employed in human subjects was underscored.

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来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
期刊介绍: Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.
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