Houston J B, Levy G
J Pharmacol Exp Ther. 1976 Aug;198(2):284-94.
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.
就水杨酰胺与抗坏血酸之间的相互作用而言，研究了给药途径对竞争性药物生物转化相互作用的影响。此前在人体中的研究表明，这种相互作用涉及对可用硫酸盐的竞争以及随后对药物硫酸盐形成的抑制。成年大鼠单独接受水杨酰胺（静脉注射100mg/kg或口服500mg/kg）或与抗坏血酸（静脉注射或口服500mg/kg）一起接受。测定了水杨酰胺、水杨酰胺葡萄糖醛酸苷和水杨酰胺硫酸盐的血浆浓度和尿排泄率随时间的变化。对于静脉注射水杨酰胺，静脉注射抗坏血酸导致水杨酰胺硫酸盐形成适度减少，从而使水杨酰胺的体内清除率降低。口服维生素的作用更为明显。该维生素对水杨酰胺的表观分布容积及其结合物的肾清除率没有影响。对于口服水杨酰胺，口服抗坏血酸导致水杨酰胺硫酸盐形成和水杨酰胺体内清除率非常明显地降低，而静脉注射维生素几乎没有影响或没有影响。这些观察结果与以下假设一致，即竞争性药物生物转化相互作用的程度作为浓度的函数，在相互作用物口服共同给药时最为明显，这是由于它们在首过期间在肠壁和肝脏中的高浓度。
