POTENTIAL CANCEROSTATIC BENFLURON IS METABOLIZED BY PEROXIDASE - IN-VITRO BIOTRANSFORMATION OF BENFLURON BY HORSERADISH-PEROXIDASE

Horseradish peroxidase (HRP) was used to investigate whether benfluron (a potential cytostatic drug) can be biotransformed extra-hepatically by systems other than flavin-containing monooxygenase and cytochromes P450. Three types of incubation mixtures differring in buffers (Na-ph osphate buffer 50 mmol/l, pH 6.8 and 8.4 and Tris-HCl buffer 25 mmol/l , pH 7.5) were tested. The amount of N-demethylated benfluron (demB) f ormed was significantly higher (up to 4 times in the Na-phosphate buff er, pH 8.4, and 5 times in the Na-phosphate buffer, pH 6.8, and in the Tris-HCl buffer, pH 7.5) compared to control experiments. The highest yields of demB were obtained with the moderately alkaline Na-phosphat e buffer (50 mmol/l, DH 8.4). The concentration of demB increased duri ng thirty minutes of incubation, and then remained constant through th e end of two-hour incubation. The results support the hypothesis that benfluron can be metabolized extra-hepatically by N-demethylation reac tion catalyzed by peroxidases.