Use of hepatocyte cultures for preliminary metabolism and cytotoxicity studies of a new anti-hypertensive agent, oxaminozoline

Abstract

1. Adult rat hepatocytes co-cultured with rat liver epithelial cells were used to evaluate chronic cytotoxicity of a new α₂ agonist, oxaminozoline (S-3341-3) compared to that of clonidine. The same maximum non-toxic concentration (25 μg per ml of medium) was found for both drugs after a daily treatment for 12 days.

2. Oxaminozoline metabolism was analysed in short-term hepatocyte cultures. Four metabolites resulting from oxidation or hydrolysis of the parent drug were identified. Three of the metabolites were identical to those reported in vivo. The presence of an additional minor metabolite in culture may be due to the higher metabolic rate of the drug in this model system.