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. Howev
er, the results obtained in-vivo suggested that very low amounts of drug re
ach the portal circulation after oral dosing. This could imply extensive bi
nding to the mucosa or metabolism in the intestinal wall. The presence of h
igher 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 bioava
ilability of centpropazine and its analogues.