科学家已经开发并采用了各种模型来研究肠淋巴吸收。一种方法涉及使用特定的阻断剂来影响乳糜微粒介导的药物的淋巴吸收。目前使用的模型包括pluronicL-81,嘌呤霉素,长春花生物碱,秋水仙碱,和环己酰亚胺.这篇评论对所使用的各种模型进行了全面的分析,评估现有报告,同时描绘当前研究的差距。它还通过讨论的模型探讨了肠淋巴摄取途径及其阻断的药代动力学相关方面。PluronicL-81具有可逆效应,最小的毒性,和独特的行动模式。然而,它缺乏乳糜微粒通路阻断的临床报道,可能是由于浓度低。嘌呤霉素和长春花生物碱,虽然有毒性记录,缺乏关于它们在药物肠道淋巴吸收中应用的信息。其他长春花生物碱在影响甘油三酸酯谱方面显示出希望,并代表了作为阻断剂进行测试的可能试剂。秋水仙碱和环己酰亚胺,广泛应用于药物开发,已经证明了疗效,与环己酰亚胺优选低毒性。然而,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.该审查还遵循了口服淋巴靶向药物从摄入到排泄的完整旅程,提供了一个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,说明了尿液数据作为一种非侵入性方法来测量通过肠淋巴管吸收药物的可能应用,强调了在人类受试者中使用特定阻断剂时药物相互作用的可能性。
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.