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Absorption characteristics of compounds with different molecular weights after application to the unilateral kidney surface in rats

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Title: Absorption characteristics of compounds with different molecular weights after application to the unilateral kidney surface in rats
Authors: Nishida, Koyo / Tomiyama, Naoki / Mukai, Takahiro / Nakashima, Mikiro / Sasaki, Hitoshi / Nakamura, Junzo
Issue Date: Nov-2004
Publisher: Elsevier
Citation: European Journal of Pharmaceutics and Biopharmaceutics, 58 (3), 705-711, 2004
Abstract: The aim of the present study is to clarify the absorption mechanism of a drug from the kidney surface membrane in rats. We studied the absorption characteristics of phenolsulfonphthalein (PSP) and other compounds with different molecular weights after their application to the rat kidney surface in vivo, employing a cylindrical diffusion cell (i.d. 6 mm, area 0.28 cm2). The time course of free PSP amounts remaining in the diffusion cell obeyed first-order kinetics at a dose of 1 mg, and its rate constant ka was calculated to be 0.0137 min?1. Absorption ratios of PSP in 4 h were calculated (from the amount recovered from the diffusion cell) to be 91.4, 96.4 and 97.7% at doses of 0.5, 1 and 1.5 mg, respectively. The area under the curve for the plasma concentration profile of free PSP was proportional to the application dose. It is thus suggested that the absorption process of PSP from the rat kidney surface does not approach saturation at a dose of 1.5 mg. Also, no significant difference was seen in the ka values within the dose range of 0.5?1.5 mg, which were estimated by curve-fitting the plasma concentration profiles of free PSP in a two-compartment model with first-order absorption. Furthermore, we examined the importance of molecular weight on the absorption from the kidney surface using fluorescein isothiocyanate-dextrans (FDs) with molecular weights of 4400 (FD-4), 11,000 (FD-10), 40,500 (FD-40) or 69,000 (FD-70), including the organic anions bromphenol blue and bromosulfonphthalein. The absorption ratios of FDs from the rat kidney surface in 6 h decreased with an increase in the molecular weight (76.1% for FD-4, 54.4% for FD-10, 11.5% for FD-40 and 3.9% for FD-70). A linear relationship was observed between ka and the reciprocal value of z the square root of the molecular weight of these compounds. The limit of absorption from the rat kidney surface was extrapolated to be at a molecular weight of approximately 130,000.
Keywords: Absorption / Kidney surface / Rat / Molecular weight / Pharmacokinetics / Targeting
URI: http://hdl.handle.net/10069/6483
ISSN: 09396411
DOI: 10.1016/j.ejpb.2004.04.016
PubMed ID: 15451548
Relational Links: http://dx.doi.org/10.1016/j.ejpb.2004.04.016
Rights: Copyright © 2004 Elsevier B.V. All rights reserved.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/6483

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