SMALL-INTESTINAL SULFOXIDATION OF ALBENDAZOLE

1. The in vitro sulphoxidation of Albendazole (ABZ) by rat intestinal microsomes has been examined. The results revealed intestinal sulphoxidation of ABZ by intestinal microsomes in a NADPH-dependent enzymatic system. The kinetic constants for sulphoxidase activity were V-max=46pmol/min/mg protein and Michaelis constant K-m=6.8 mu M. 2. The possible effect of inducers (Arochlor 1254 and ABZ pretreatment) and inhibitors (erythromycin, methimazole, carbon monoxide and fenbendazole), was also studied. In rat pretreated with Arochlor 1254, V-max was 52pmol/min/mg protein, whereas oral administration of ABZ increased the intestinal sulphoxidation of the drug, V-max being 103 pmol/min/mg protein. 3. Erythromycin did not change the enzymatic bioconversion of ABZ, but methimazole and carbon monoxide inhibited the enzyme activity by approximately 60 and 30% respectively. Fenbendazole (a structural analogue of ABZ) was a competitive inhibitor of the sulphoxidation process, characterized by a K-i or 69 mu M. 4. These data demonstrate that the intestinal enzymes contributing to the initial sulphoxidation of ABZ may be similar to the hepatic enzymes involved in the biotransformation process by the P450 and FMO systems, a conclusion that needs to be further established.