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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Difference in hepatic uptake kinetics of aspirin and salicylamide in rats.

Immediately after intraportal administration to rats, the ratio of liver to plasma concentrations for total aspirin was close to unity, whereas that for total salicylamide ranged from about 3 to 7. The hepatic accumulation of salicylamide appeared to be capacity-limited because the ratio decreased with increases in the dose. In vitro experiments with isolated hepatocytes indicated that aspirin was slowly transported into the hepatocytes by an apparently linear process only, while salicylamide was taken up very rapidly by both saturable and apparently linear transport processes. The cell to medium concentration ratio estimated for the initially net transported component of the unchanged drug was significantly larger with salicylamide, which give ratios from 3.5 to 19, than with aspirin which gave an almost constant value lower than 2 despite wide variations in the initial concentration. For the capacity-limited uptake process of salicylamide, the kinetic parameters were estimated as Vmax = 0.325 nmole X (mg cellular protein)-1 X sec-1 and Km = 201 microM. Among various metabolic inhibitors, 2,4-dinitrophenol (50 microM) inhibited the uptake of salicylamide most extensively. The present comparison of the in vivo and in vitro data for aspirin with those for salicylamide confirmed the previously reported difference in the hepatic first-pass effect of these two drugs.[1]


  1. Difference in hepatic uptake kinetics of aspirin and salicylamide in rats. Iwamoto, K., Furune, Y., Watanabe, J. Biochem. Pharmacol. (1984) [Pubmed]
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