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Lymphatic Transport of Drugs after Intestinal Absorption: Impact of Drug Formulation and Physicochemical Properties

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Abstract

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 (FRL) 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 FRL [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 FRL in drugs with log P < 5, which was not observed in simple formulations and oil solutions. No relation was found between FRL 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.

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Abbreviations

DTX-S-OA:

Docetaxel thioether oleate

MCT:

Medium chain triglycerides

2-MPA-TG:

1,3-dipalmitoyl-2-mycophenoloyl glycerol

LCT:

Long chain triglycerides

SCT:

Short chain triglycerides

SEDDS:

Self-emulsifying drug delivery system

SES:

Self-emulsifying system

SLN:

Solid lipid nanoparticles

SMEDDS:

Self-microemulsifying drug delivery system

SNEDDS:

Self-nanoemulsifying drug delivery system

SNEOF:

Self-nanoemulsifying oily formulation

SNESN:

Self-nanoemulsifying self-nanosuspension

TST-C5-βMe-TG:

Testosterone triglyceride prodrug

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors declare no conflict of interest. This work was supported by the Charles University Project Progres Q25 and grant No. SVV 260 523.

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  1. Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Pavel Ryšánek, Martin Šíma & Ondřej Slanař

  2. Department of Cardiovascular Surgery, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Tomáš Grus

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Ryšánek, P., Grus, T., Šíma, M. et al. Lymphatic Transport of Drugs after Intestinal Absorption: Impact of Drug Formulation and Physicochemical Properties. Pharm Res 37, 166 (2020). https://doi.org/10.1007/s11095-020-02858-0

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