Distribution of fentanyl in rats: an autoradiographic study

Unexpected respiratory depression reported to have occurred up to 2 h after neurolept analgesia with fentanyl has been proposed to be a redistribution phenomenon due to a gastro-entero systemic recirculation of fentanyl sequestered in the stomach. In the study presented here, this redistribution hypothesis was tested by employing whole-body autoradiography (WBAR) in two series of time-course experiments, designated to further elucidate the distribution of intravenously administered fentanyl which was radiolabelled in different parts of the molecule respectively. However, there was no evidence of a secondary accumulation of radioactivity in the brain. The possibility that fentanyl trapped in the stomach may be reabsorbed as it passes through the small intestines was investigated by intragastric administration of the drug. Its oral bioavailability was found to be only 1.5%. Also, evidence of a strong metabolic effect was obtained by analysis employing high performance thin-layer chromatography (HPTLC). In conclusion, the results obtained from this work do not support the hypothesis that the fentanyl rebound effect is due to a secondary rise in brain levels of the parent drug and its major metabolites, an event which could be brought about by reabsorption of fentanyl sequestered in the stomach.