Evaluation of intestinal absorption into the portal system in enterohepatic circulation by measuring the difference in portal-venous blood concentrations of diclofenac.
OBJECTIVE
We evaluated the first-pass effects in vivo by the intestine and liver during enterophepatic circulation (EHC) by simultaneously measuring the portal and venous plasma concentrations of the rat.


METHODS
The venous and upper portal blood vessels were cannulated through the jugular and the pyloric veins, respectively, to obtain simultaneously blood samples from both sites. After diclofenac was injected as a bolus through the jugular vein, the concentrations of diclofenac in the portal and jugular veins were measured at time intervals. The absorption rate from the intestinal tract into the portal system was determined using the portal-venous difference in plasma concentrations of diclofenac, considering 40% partitioning of diclofenac into erythrocytes.


RESULTS
After one hour, the plasma concentration in the portal vein was always higher than that in the jugular vein in awakening rats with intact EHC (portal-venous blood concentration difference). No portal-venous difference was observed in awakening rats with bile-duct cannulation. Therefore, it was concluded that this portal-venous concentration difference was not due to the hepatic clearance but to diclofenac reabsorption from the intestinal tract.


CONCLUSIONS
Approximately 40% of the dose of diclofenac was reabsorbed over 8 hours from the intestinal tract into the portal system. By comparing the reabsorbed amounts in the portal system and in the systemic circulation, the hepatic extraction ratio in vivo (FH) of diclofenac was estimated to be 63%.
Tabata
K
K
Faculty of Pharmaceutical Science, Kyoto University, Japan.
Yamaoka
K
K
Fukuyama
T
T
Nakagawa
T
T
D000818:Animals; D004008:Diclofenac / Q000097:blood / Q000493:pharmacokinetics*; D004764:Enterohepatic Circulation; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010599:Pharmacokinetics; D011168:Portal System / Q000378:metabolism*; D011169:Portal Vein / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004008:Diclofenac