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

Effect of route of administration on competitive drug biotransformation interaction: salicylamide-ascorbic acid interaction in rats.

The effect of route of administration on competitive drug biotransformation interactions was explored with respect to the interaction between salicylamide and ascorbic acid. Previous studies in man have shown that this interaction involves competition for available sulfate and consequent inhibition of drug sulfate formation. Adult rats received salicylamide (100 mg/kg i.v. or 500 mg/kg orally) alone or with ascorbic acid (500 mg/kg i.v. or orally). Plasma concentrations and urinary excretion rates of salicylamide, salicylamide glucuronide and salicylamide sulfate were determined as a function of time. With i.v. salicylamide, i.v. ascorbic acid caused a modest decrease of salicylamide sulfate formation and thereby of salicylamide body clearance. Orally administered vitamin had a somewhat more pronounced effect. The vitamin had no effect on the apparent volume of distribution of salicylamide and on the renal clearances of its conjugates. With orally administered salicylamide, oral ascorbic acid caused a very pronounced decrease of salicylamide sulfate formation and salicylamide body clearance, whereas intravenous vitamin had little or no effect. These observations are consistent with the assumption that the magnitude of competitive drug biotransformation interactions, being a function of concentration, is most pronounced when the interactants are co-administered orally, due to their high concentrations in the intestinal wall and liver during the first pass.[1]


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