• Toxicological Research
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• 제11권1호
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• pp.103-108
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• 1995

Rat renal proximal tubule suspension was prepared from adult male Sprague Dawley rat (250-300g) by mechanical (non-enzymatical) method and evaluated as a pontential model for mechanistic studies and early screening of nephrotoxicity, using anionic antibiotics (cephaloridine). Cephaloridine (CPL) produced an increase in LDH release into media. This release results from decrease a proximal tubule cell viability and subsequently increase the permeability of cell viability and subsequently increase the permeability of cell membrane. Since loss of intracellular potassium and ATP into media is the sign of disruption of cell membrane, especially basolateral membrane (BLM), CPL induced proximal tubule cell compromise also appear be associated with BLM, maybe $Na^+-K^+$ ATPase. Also seen was significant depression in brush border membrane (BBM) ALP activity and no significantly increase in BBM GGT activities. The inhibition of typical anion, PAH accumulation (especially, CPL 5 mM) and cation, TEA (especially, 4hours incubation) were seen dose dependently. This is because of CPL accumulation in renal proximal tubule and increase of cytotoxicity.

• Journal of Pharmaceutical Investigation
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• 제17권4호
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• pp.205-211
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• 1987

Renal dysfunction can have pronounced effects on the pharmacokinetic and pharmacodynamic characteristics of drugs. Because the exploration of these effects in patients may be limited by ethical and practical considerations, it often become necessary to perform studies on animals with experimental renal failure(ERF). ERF was produced in rats by the administration of uranyl nitrate, glycerol, salicylate, gentamicin and folate in this study. Changes in glomerular filtration rate(GFR) and renal secretion clearance of tetraethylammonium bromide$(CL^{scn}_{TEA})$, together with morphological changes of kidney cortex were evaluated and compared among ERF models. GFR(or glomeruli) and $CL^{scn}_{TEA}$(or renal tubules) were not damaged parallelly in some ERF model rats. Therefore, it seemed to be necessary to adjust dosage regimen of some basic drugs like TEA in renal dysfunction considering the functional changes of renal secretion in addition to glomerular filtration.

• 약학회지
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• 제27권1호
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• pp.21-28
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• 1983

Distribution volume (Vd$_{ss}$ ) of a model basic drug, tetraethylammonium bromide (TEA) at a steady-state decreased sinificantly in glycerol and uranium-renal failure rats. Assuming carrier-mediated transport of TEA into tissues, the theoretical $Vd_{ss}$ of TEA decreases in an exponential way as the plasmal concentration of TEA increases. The relationship between $Vd_{ss}$ and plasma concentration of TEA in the experimental renal failure (ERF)-rats was similar. Therefore, the decrease in $Vd_{ss}$ of TEA in the ERF-rats seemed to be due to the saturation of the carrier system that are responsible for the tissue distribution of TEA, by the elevated plasma concentration of TEA in the ERF-rats. ERF was induced to rats with glycerol, folate, salicylate, uranium and gentamicin, respectively..