Archiv der Pharmazie (Weinheim) 1989-07-01

[Biotransformation of benzamidine and benzamidoxime by microsomal enzymes of the rabbit].

B Clement, M Zimmermann, S Schmitt

Index: Arch. Pharm. (Weinheim) 322(7) , 431-5, (1989)

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Abstract

At pH 7.4 neither benzamidine (1) is ring-hydroxylated nor benzamidoxime (2) is N-hydroxylated, reduced or ring-hydroxylated by aerobic incubations with microsomal fractions (12000 g supernatant, microsomes) of rabbit liver homogenates and NADPH. Products of hydrolytic processes are also not detected. A very long incubation period and a pH 6.3 are necessary for the detection of a slight reduction of benzamidoxime (2) to benzamidine (1). Results are obtained by use of synthetic reference material and by newly developed HPLC methods. Thus, kinetic studies of the microsomal N-hydroxylation of benzamidine (1) to benzamidoxime (2) in the presence of N-methylbenzamidine (3) performed at pH 7.4 are not influenced by other transformations and provide evidence for the involvement of the same isoenzyme of cytochrome P-450 for both the N-hydroxylation of 1 and the N-dealkylation of 3.