Evaluation of pharmacokinetics, brain levels and protein binding of centpropazine in rats

The pharmacokinetics of centpropazine (CNPZ), an antidepressant, was studied in rats. CNPZ was administered to groups of rats ( n=3 to 5) via oral (40 mg/kg), intravenous (5 mg/kg), intraperitoneal (5 mg/kg) and intraduodenal (4 and 8 mg/kg) routes. The AUC s of CNPZ were estimated and the bioavailabilities were calculated. CNPZ was characterized by a short elimination half‐life (39.5 min), a high clearance (118 ml/min/kg) and a relatively large volume of distribution (1945 ml/kg) after intravenous administration. After oral administration CNPZ exhibited a very low oral bioavailability (∼0.2%). The total first pass effect ( E git+liver ) was calculated as 98.7%. The bioavailability of CNPZ was similar when administered by intraduodenal and oral routes. CNPZ readily penetrated into the brain and reached C max by 30 min post oral dosing. About 92.0%±0.8% of the drug was bound to serum proteins. Low oral bioavailability of CNPZ following oral administration is likely due to its metabolism by intestinal mucosa and liver. Copyright © 2004 John Wiley & Sons, Ltd.