Interspecies variation in the metabolism of zoniporide by aldehyde oxidase

Abstract

1. Aldehyde oxidase (AO) is a cytosolic enzyme that contributes to the Phase I metabolism of xenobiotics in human and preclinical species.

2. Current studies explored in vitro metabolism of zoniporide in various animal species and humans using S9 fractions. The animal species included commonly used pharmacology and toxicology models and domestic animals such as the cat, cow or bull, pig and horse.

3. In addition, gender and strain differences in some species were also explored.

4. All animals except the dog and cat converted zoniporide to 2-oxozoniporide (M1).

5. Michael-Menten kinetic studies were conducted in species that turned over zoniporide to M1.

6. Marked differences in K_M, V_max and Cl_int were observed in the oxidation of zoniporide.

7. Although the K_M and V_max of zoniporide oxidation in male and female human S9 was similar, some gender difference was observed in animals especially, in V_max.

8. The domestic animals also showed marked species differences in the AO activity and affinity toward zoniporide.

Keywords::

• Aldehyde oxidase
• species differences
• zoniporide