A new aspect of tolbutamide metabolism in the rabbit: the role of 1-butyl-3-(p-formylphenyl)sulphonylurea

Author:

Washio Kanetoshi1,Makaya Osami1,Sasaki Hitoshi1,Nishida Koyo1,Nakamura Junzo1,Shibasaki Juichiro1

Affiliation:

1. School of Pharmaceutical Sciences, Nagasaki University, 1–14 Bunkyo-machi, Nagasaki 852, Japan

Abstract

Abstract We investigated the metabolism of tolbutamide by using synthetic 1-butyl-3-(p-formylphenyl)sulphonylurea (ATB), an intermediate in the metabolic pathway of tolbutamide. ATB (40 mg kg−1) administered intravenously to rabbits was oxidized to 1-butyl-3-(p-carboxyphenyl)sulphonylurea (CTB) and also reduced to 1-butyl-3-(p-hydroxymethylphenyl)sulphonylurea (HMTB). Therefore, it is likely that in the metabolism of tolbutamide, the oxidation of HMTB to ATB involved the reverse reaction, suggesting the reduction of ATB to HMTB. The oxidation of ATB to CTB was inhibited by disulfiram pretreatment. ATB was detected in the blood following intravenous administration of HMTB in rabbits pretreated with disulfiram. These results, confirm that ATB is an intermediate in the oxidative metabolism of tolbutamide in the rabbit.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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