Destruction of chlorpromazine during absorption in the rat in vivo and in vitro.

Abstract

1. Concentrations of total radioactivity in plasma of rats given intravenous and oral (35)S-chlorpromazine, were similar. Concentrations of unchanged drug, however, were lower after oral doses.2. Chlorpromazine circulated in solution through isolated loops of rat intestine was rapidly absorbed by the tissue. Measurements of glucose transport and histological examination indicated that the tissue was intact. In these in vitro experiments some of the chlorpromazine was converted to products, which together with unchanged drug, were partly retained in the intestinal wall and partly transferred to the serosal side of the tissue. Observations at three concentrations supported the hypothesis that transfer of unchanged drug occurred by passive diffusion.3. Conversion of chlorpromazine to metabolites in the intestine in vivo, would account for the differences in concentrations of chlorpromazine and total radio-activity in plasma after oral doses.