Drug Absorption, Metabolism, and Excretion. IX. Some New Aspects of Pharmacokinetics on Tolbutamide in Rabbits

概要

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Pharmacokinetics on the metabolism and excretion of tolbutamide (TB) following the rapid intravenous injection of TB was investigated in rabbits based on the kinetic model where TB is first oxidized to 1-butyl-3-p-hydroxymethylphenylsulfonylurea (HTB), which is secondly converted to 1-butyl-3-p-carboxyphenylsulfonylurea (CTB) and both the metabolites are excreted in urine. It was found that binding of TB to plasma proteins and/or blood cells could not be neglected and the excretion of HTB formed in body would be well interpreted by assuming an intervenient compartment between blood and urine. Furthermore, pharmacokinetics of HTB was investigated after the administration of HTB to rabbits. It became clear that the amount of CTB formed in body after the administration of HTB was far smaller than that formed in body after the administration of TB indicating that the assumption that a metabolite administered per se would behave in the same manner as the metabolite formed in body from its precursor is not always free from criticism, though it has been undoubtedly employed to many pharmacokinetic studies of drugs. On the contrary, it was suggested that CTB administered per se would behave samely in body as CTB formed through metabolic reaction from TB or HTB by the experiment in which rabbits were given CTB intravenously.
社団法人日本薬学会の論文
1973-08-25