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  • 1
    ISSN: 1432-1912
    Keywords: Mutant rats ; Liver ; Intestine ; Kidney ; 1-Naphthol-β-d-glucuronide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR− rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol-β-d-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR− rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR− rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR− rat when compared with the Wistar rat. Thus, the genetic defect in the TR− rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Intestinal absorption ; 1-Naphthol ; Glucuronidation ; Rat ; Albumin binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using an isolated vasculary perfused rat small intestine we studied the role of luminal flow rate and intraluminal binding on the absorption of 1-naphthol (1-N) and the intestinal metabolism of 1-N to 1-naphthol-β-d-glucuronide (1-NG). Raising the luminal perfusion rate resulted in a decrease in the luminal 1-N extraction ratio and an increase in the luminal 1-N clearance Cl lum. The dependency of Cl lum on flow rate appeared to conform to a convective diffusion model. A differential susceptibility of 1-N absorption and the total 1-NG appearance to the luminal flow rate resulted in a flow-dependent first-pass effect of 1-N. Next, the effect of intraluminal binding on 1-N disposition was studied in experiments in which albumin was added to the luminal perfusion fluid. The unbound concentration, as the driving force for the uptake of 1-N, seems not to be rate-limiting for the appearance of 1-NG. The total appearance of 1-NG in the presence of albumin was greater than would be anticipated from the free concentration of 1-N. As a result the extent of presystemic extraction increased with increasing albumin concentration. The precise mechanisms responsible for the phenomenona are not entirely clear. Consideration of the heterogeneity in the glucuronidation capacity along the rat small intestine and along the crypt-villus axis can help to explain the obtained results.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 239-245 
    ISSN: 1432-1912
    Keywords: Intestinal absorption ; Vascular perfusion ; Glucuronidation ; 1-Naphthol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using the isolated vascularly fluorocarbon emulsion perfused rat small intestine some factors which determine the extent of the intestinal glucuronidation of 1-naphthol to 1-naphthol-β-d-glucuronide were studied. Increasing the luminal 1-naphthol concentration resulted in a concomitant increase in the 1-naphthol appearance in the vascular perfusate. In contrast, the total appearance of 1-naphthol-β-d-glucuronide increased less than proportional to the increase in the luminal 1-naphthol concentration. About 88% of the total amount of 1-naphthol-β-d-glucuronide excreted was released into the vascular perfusate. The capacity-limited intestinal glucuronide efflux is most likely due to saturation of the excretory mechanism for 1-naphthol-β-d-glucuronide. Decreasing the vascular flow rate influenced both the appearance of 1-naphthol and 1-naphtol-β-d-glucuronide in the vascular perfusate, whereas the appearance of 1-naphthol-β-d-glucuronide in the luminal perfusate was essentially flow-independent. A noradrenaline-induced change in the haemodynamic state of the vascular bed (with the total flow kept constant) resulted in a marked decrease in the 1-naphthol vascular concentration. The vascular 1-naphthol-β-d-glucuronide concentration was only slightly affected. These results indicate that changes in blood flow and blood flow distribution within the intestinal wall can affect the extent of presystemic intestinal metabolism by interfering with the absorption of the parent compound and the efflux of formed conjugates. These parameters can be of paramount importance for causing variable intestinal first-pass effects of drugs in vivo.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 7 (1985), S. 280-284 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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