Evaluation of absorbability of centpropazine in rats: in-situ and in-vivo approaches

Intestinal absorption of centpropazine was studied in rats by both in-situ (closed-loop method) and in-vivo (portal-venous difference) approaches. The drug was found to be well absorbed from solution in in-situ studies. However, the results obtained in-vivo suggested that very low amounts of drug reach the portal circulation after oral dosing. This could imply extensive binding to the mucosa or metabolism in the intestinal wall. The presence of higher a mounts of metabolites in the portal vein compared with the inferior vena cava samples signal their formation in the gastrointestinal tract or enterohepatic recirculation. These findings will be useful in incorporating suitable structural and formulation modifications for enhancing the bioavailability of centpropazine and its analogues.