A new aspect of tolbutamide metabolism in the rabbit: the role of 1-butyl-3-(p-formylphenyl)sulphonylurea.
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.
Washio
K
K
School of Pharmaceutical Sciences, Nagasaki University, Japan.
Makaya
O
O
Sasaki
H
H
Nishida
K
K
Nakamura
J
J
Shibasaki
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004221:Disulfiram / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction; D011817:Rabbits; D014044:Tolbutamide / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000652:urine; D000096926:Benzenesulfonamides
D004221:Disulfiram; D014044:Tolbutamide; C006913:carboxytolbutamide; C031014:hydroxymethyltolbutamide; D000096926:Benzenesulfonamides; C081051:1-butyl-3-(4-formylphenyl)sulfonylurea