VUFB-15496

The disposition of cloflumide (VUFB 15496), 2-chloro-7-fluoro-10 [4-(carbamoylethyl)piperazino]-10,11-dihydrodibenzo [b,f] thiepin methansulfonate, a new neuroleptic agent, following single oral and intravenous dose was studied in the rat using radiotracer techniques. [3H]Cloflumide was almost completely absorbed from the gastrointestinal tract; peak plasma levels of the parent drug were attained within 4 h of oral drug administration. The mean residence time of the unchanged drug was 2.75 h after intravenous administration. The total neuroleptic activity in plasma determined by radioreceptor assay paralleled with plasma cloflumide level indicating that the dopamine inhibiting action is mediated solely by the parent drug. Concentration of radioactive substances was high in the liver and kidneys; in the brain was slightly higher than blood level. Total radioactive meterial as well as unchanged cloflumide were mostly excreted in feces (87 and 10%, respectively). At 3 days postdosing, 96% of the administered dose was recovered.