[Biotransformation of benzamidine and benzamidoxime by microsomal enzymes of the rabbit].
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.
Clement
B
B
Zimmermann
M
M
Schmitt
S
S
D000578:Amidines / Q000493:pharmacokinetics*; D000818:Animals; D001550:Benzamidines / Q000493:pharmacokinetics*; D001711:Biotransformation; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D011817:Rabbits
D000578:Amidines; D001550:Benzamidines; C053561:benzamidoxime
Biotransformation des Benzamidins und des Benzamidoxims durch mikrosomale Enzyme vom Kaninchen.