Purpose

To provide a comprehensive and up-to-date overview focusing on the extent of lymphatic transport of drugs following intestinal absorption and to summarize available data on the impact of molecular weight, lipophilicity, formulation and prandial state.

Methods

Literature was searched for in vivo studies quantifying extent of lymphatic transport of drugs after enteral dosing. Pharmacokinetic data were extracted and summarized. Influence of molecular weight, log P, formulation and prandial state was analyzed using relative bioavailability via lymph (F_RL) as the parameter for comparison. The methods and animal models used in the studies were also summarized.

Results

Pharmacokinetic data on lymphatic transport were available for 103 drugs. Significantly higher F_RL [median (IQR)] was observed in advanced lipid based formulations [54.4% (52.0)] and oil solutions [38.9% (60.8)] compared to simple formulations [2.0% (27.1)], p < 0.0001 and p = 0.004, respectively. Advanced lipid based formulations also provided substantial F_RL in drugs with log P < 5, which was not observed in simple formulations and oil solutions. No relation was found between F_RL and molecular weight. There were 10 distinct methods used for in vivo testing of lymphatic transport after intestinal absorption so far.

Conclusion

Advanced lipid based formulations provide superior ability to increase lymphatic absorption in drugs of various molecular weights and in drugs with moderate to low lipophilicity.

中文翻译：

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肠道吸收后药物的淋巴运输：药物配方和理化性质的影响。

目的

提供有关肠道吸收后药物的淋巴转运程度的全面而最新的概述，并总结有关分子量，亲脂性，配方和餐后状态影响的可用数据。

方法

搜寻文献进行体内研究以量化肠内给药后药物的淋巴转运程度。提取并总结了药代动力学数据。以相对生物利用度（淋巴）（F _RL）为比较参数，分析了分子量，log P，制剂和膳食状态的影响。还总结了研究中使用的方法和动物模型。

结果

已有103种药物的淋巴转运药代动力学数据。与简单配方[2.0％（27.1）]相比，高级脂质基配方[54.4％（52.0）]和油溶液[38.9％（60.8）]中观察到的F _RL [中位数（IQR）]高，p  <0.0001和p 分别为0.004。先进的基于脂质的制剂还为log P <5的药物提供了较高的F _RL，这在简单的制剂和油溶液中未观察到。在F _RL和分子量之间未发现任何关系。迄今为止，有10种不同的方法用于肠道吸收后体内淋巴转运的体内测试。

结论

先进的基于脂质的制剂在各种分子量的药物和中度至低亲脂性药物中具有增强淋巴吸收的卓越能力。