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 > 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.
Similar content being viewed by others
REFERENCES
E. Tomlinson. Adv. Drug Deliv. Rev. 1:127–131 (1987).
J. H. Lewis. JAMA 76:1342–1345 (1921).
M. E. Field and C. K. Drinker. Am. J. Physiol. 97:40–51 (1931).
J. N. Weinstein, M. A. Steller, D. G. Covell, O. D. Holton, A. M. Keenan, S. M. Sieber, and R. J. Parker. Cancer Treat. Rep. 68:257–264 (1984).
A. Supersaxo, W. Hein, H. Gallati, and H. Steffen. Pharm. Res. 5:472–476 (1988).
S. Pestka. Arch. Biochem. Biophys. 221:1–37 (1983).
J. G. Hall and B. Morris. Q. J. Exp. Physiol. 47:360–369 (1962).
M. Miyasaka and Z. Trnka. In I. Lefkovits, and B. Pernis (eds.), Immunological Methods, Vol. III, Academic Press, New York, 1985, p. 403.
H. Gallati. J. Clin. Chem. Clin. Biochem. 22:907–914 (1982).
S. Muranishi, K. Takada, H. Yoshikawa, and M. Murakami. In S. S. Davies, L. Illum, and E. Tomlinson (eds.), Delivery Systems for Peptide Drugs, Plenum Press, New York and London, 1986, pp. 177–189.
C. C. C. O'Morchoe and P. J. O'Morchoe. Lymphology 20:205–209 (1987).
L. V. Leak. J. Cell Biol. 50:300–323 (1971).
G. Poste. Proc. Int. Symp. Control. Rel. Bioact. Mater. 15:1–2 (1988).
V. Bocci. Immunol. Today 6:7–9 (1985).
V. Bocci. Immunology 64:1–9 (1988).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Supersaxo, A., Hein, W.R. & Steffen, H. Effect of Molecular Weight on the Lymphatic Absorption of Water-Soluble Compounds Following Subcutaneous Administration. Pharm Res 7, 167–169 (1990). https://doi.org/10.1023/A:1015880819328
Issue Date:
DOI: https://doi.org/10.1023/A:1015880819328