Objective To investigate the variation of fentanyl concentration and the gene expression and activity of rat intestinal cytochrome P450 3A1 in anhepatic phase.  Methods The experiment was comprised of 2 steps. Step 1: The rats were randomly divided into experimental group (group A2

underwent occlusion of the hepatic portal) and control group (group A1)

with 10 rats in each group. Fentanyl blood concentration was analyzed by LC/MS/MS. Step 2: The rats were randomly divided into group B1 (control)

group B2 and group B3 (the rats underwent devascularization of the hepatic portal for 30 or 60 min). The levels of CYP3A1 in rat small intestine were assessed with RT-PCR and the enzymic activity of CYP3A1 was detected by fluorometry.  Results Fentanyl concentration in anhepatic phase dropped more slowly in group A2 than group A1 (P0.05)

but still remained descending. The gene expression and the enzymic activity of CYP3A1 in rat small intestine were significantly higher in group B2 and group B3 than those in group B1 (P0.05). The gene expression of CYP3A1 in rat small intestine between group B2 and group B3 was not significantly different.  Conclusion Fentanyl metabolism is mainly in the liver. Higher gene expression and enzymic activity of intestinal CYP3A1 occurs in rats in anhepatic phase than the rats whose hepatic portal is occluded

which may be one of the possible mechanisms for extrahepatic metabolism of fentanyl in anhepatic phase.