Absorption characteristics of dextrans with different molecular weights from the liver surface membrane in rats: implications for targeting to the liver

Journal of Drug Targeting
K NishidaJ Nakamura

Abstract

We examined the importance of molecular weight on the absorption from the liver surface in rats using fluorescein isothiocyanate-dextrans (FDs) with molecular weights of 4,400 (FD-4), 9,300 (FD-10), 40,500 (FD-40) or 69,000 (FD-70). After application of FDs (5 mg) to the rat liver surface employing a cylindrical glass cell (i.d. 9 mm), each FD appeared gradually in the plasma, and the in vivo behavior was explained by two-compartment model with first-order absorption. The absorption ratios of FDs from the rat liver surface at 6 h, calculated from the amount recovered from the glass cell, decreased with an increase in the molecular weight (44.5% for FD-4, 29.3% for FD-10, 5.1% for FD-40 and 2.2% for FD-70). A linear relationship was observed between the absorption rate constant and the reciprocal value with square root of molecular weight of the model compounds. The limit of absorption from the rat liver surface was extrapolated to be at a molecular weight of 70,000. Furthermore, absorbed FDs were accumulated in the liver, as high liver/plasma concentration ratio as compared with that of i.v. administration. We clarified the molecular weight dependence of drug absorption from the liver surface in rats. Moreover, the liver surfac...Continue Reading

References

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Citations

Nov 10, 2000·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·K NishidaJ Nakamura
Jun 27, 2002·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Takashi TamuraOsamu Ike
Nov 7, 2002·Biological & Pharmaceutical Bulletin·Takahiro MukaiJunzo Nakamura
May 3, 2007·Biological & Pharmaceutical Bulletin·Junzo NakamuraKoyo Nishida
Aug 23, 2003·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Koyo Nishida
Aug 5, 2009·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Koyo Nishida
Feb 5, 2014·Biological & Pharmaceutical Bulletin·Haruna HirataKoyo Nishida
Apr 16, 2011·The Journal of Pharmacy and Pharmacology·Koyo NishidaJunzo Nakamura
Sep 29, 2004·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Koyo NishidaJunzo Nakamura
Aug 7, 2002·The Journal of Pharmacy and Pharmacology·Koyo NishidaJunzo Nakamura

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