Effect of Molecular Weight on the Lymphatic Absorption of Water-Soluble Compounds Following Subcutaneous Administration
Abstract
The lymphatic absorption of four water-soluble compounds with different molecular weights (MW) was determined by measuring their cumulative recovery in lymph draining from the site of s.c. administration in sheep. The cumulative recoveries (% of dose, mean +/- SD; N = 3) were 4.0 +/- 1.5 (5-fluoro-2'-deoxyuridine, MW 246.2), 21.0 +/- 7.1 (inulin, MW 5200), 38.6 +/- 6.7 (cytochrome c, MW 12,300), and 59.5 +/- 7.7 [human recombinant interferon (rIFN) alpha-2a, MW 19,000], respectively. Our data show that in the investigated MW range, there is a linear relationship between the molecular weight and the proportion of the dose absorbed lymphatically. An increase in molecular weight results in an increased lymphatic absorption. Molecules with MW greater than 16,000 are absorbed mainly by the lymphatics which drain the application site. The knowledge gained in this investigation may help to improve the mode of administration and therapeutic efficacy of endogenous proteins whose targets are lymphoid cells (e.g., interferons, interleukins). Practical implications for the clinical use of such proteins are discussed.
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Subcutaneously injected therapeutic proteins typically have a slow absorption rate from the subcutaneous extracellular matrix, with Cmax levels below those achieved with intravenous dosing.
“whereas the pharmacokinetic profile of subcutaneously injected therapeutic proteins is typically characterized by a slow absorption rate from the subcutaneous extracellular matrix with Cmax levels below those achieved with intravenous dosing.”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [71]
The absorption pattern of macromolecules into the blood is a consequence of their limited permeability across the vascular endothelia.
“This absorption pattern of macromolecules into the blood is a consequence of their limited permeability across the vascular endothelia”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [71]
The lymphatics provide an alternative absorption pathway into the circulation system for macromolecules.
“therefore, the lymphatics provide an alternative absorption pathway into the circulation system [70, 71].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [71]
Following subcutaneous injection, biotherapeutics with molecular weights of > 20 kDa exhibit limited transport into blood capillaries and cross into the systemic circulation predominantly via the lymphatics.
“Unlike small molecules, biotherapeutics with molecular weights of > 20 kDa exhibit limited transport into the blood capillaries and cross into the circulation system predominantly via the lymphatics [10, 71].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [71]
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References 14 · Cited by 386
- Authors
- Supersaxo, A., Hein, W. R., & Steffen, H.
- Affiliations
- F. Hoffmann-La Roche AG (CH)
- ORCID
- Hein, Wayne R.
- Venue
- Pharmaceutical Research
- Published
- 1990-02
- Volume
- 7
- Issue
- 2
- Pages
- 167-169
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W1586699825
- Cited by
- 386
- References
- 14
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 25 · 2023: 20 · 2022: 25 · 2021: 29 · 2020: 21 · 2019: 19 · 2018: 18 · 2017: 9 · 2016: 11 · 2015: 20 · 2014: 10 · 2013: 20 · 2012: 25
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- lymphatic absorption, molecular weight, subcutaneous administration, water-soluble compounds, lymphatic drainage, 5-fluorodeoxyuridine, inulin, cytochrome c, interferon alfa-2a, sheep, lymphatic drug delivery
- MeSH terms
- Absorption, Animals, Chemistry, Physical, Female, Floxuridine, Injections, Subcutaneous, Insulin, Interferon Type I, Lymphatic System, Male, Molecular Weight, Recombinant Proteins, Sheep, Solubility, Chemical Phenomena
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