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Delivery advantage to the unilateral kidney by direct drug application to the kidney surface in rats and pharmacokinetic verification based on a physiological model


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Title: Delivery advantage to the unilateral kidney by direct drug application to the kidney surface in rats and pharmacokinetic verification based on a physiological model
Authors: Nishida, Koyo / Kamenosono, Manabu / Kuma, Akiko / Fumoto, Shintaro / Mukai, Takahiro / Nakashima, Mikiro / Sasaki, Hitoshi / Nakamura, Junzo
Issue Date: May-2005
Publisher: Taylor & Francis
Citation: Journal of Drug Targeting, 13 (4), 215-223, 2005
Abstract: The objective of this study was to evaluate the drug delivery advantage to the unilateral kidney by direct drug application to the rat kidney surface based on a physiological pharmacokinetic model. Under anesthesia, a cylindrical diffusion cell (i.d. 6 mm, area 0.28 cm(2)) was attached to the right kidney surface in rats. Phenolsulfonphthalein (PSP), an organic anion chosen as a model compound, was added into the diffusion cell. The free PSP concentration in the right (applied) kidney after application to the right kidney surface at a dose of 1 mg was significantly higher than that of the left (non-applied) kidney until 60 min after application. Similarly, the urinary excretion rate of free PSP from the applied kidney was much faster than that from the non-applied kidney, with a 2.6 times larger excreted amount in 240 min. These results imply the possibility that a considerable drug delivery advantage to the unilateral kidney could be obtained after direct absorption from the kidney surface. This tendency was also observed at the other application doses of 0.3 and 1.5 mg. On the other hand, fluorescein isothiocyanate dextran (Mw 4400, FD-4) was equally excreted into the urine from each kidney and the renal concentrations in the applied and non-applied kidneys were almost the same, possibly due to the involvement of passive transport for the absorbed FD-4, i.e. glomerular filtration. The computer simulations of free PSP concentrations in the plasma and each kidney based on a physiological model after kidney surface application were consistent with the respective experimental data. Moreover, the delivery advantage of kidney surface application of PSP was verified by its comparison with other routes such as i.v. and i.a. administrations.
Keywords: Kidney surface / targeting / unilateral delivery / physiological model / pharmacokinetics
URI: http://hdl.handle.net/10069/6488
ISSN: 1061186X
DOI: 10.1080/10611860500159097
PubMed ID: 16051533
Relational Links: http://dx.doi.org/10.1080/10611860500159097
Rights: This is an electronic version of an article published in J Drug Target. 2005 May13(4):215-23. the Journal of Drug Targeting is available online at: http://taylorandfrancis.metapress.com/openurl.asp?genre=article&id=doi:10.1080/10611860500159097.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/6488

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