Absorptive clearance of carbamazepine and selected metabolites in rabbit intestine

The intestinal permeability of carbamazepine, an antiepileptic drug, was examined as a function of intestinal site (duodenojejunum vs colon). A "through-and-through" in situ intestinal perfusion technique was adopted using the rabbit as an animal model. Coperfusion of the 10,11-epoxide and the 10,11-transdihydrodiol metabolites along with carbamazepine allowed for an examination of the effect of lipophilicity on intestinal permeability when molecular weight differences are negligible. Our results showed that carbamazepine is absorbed from rabbit duodenojejunum as well as the colon, which may explain the prolonged absorption behavior observed in humans. Also, the absorptive clearance of compounds having similar molecular weights is dependent not only on the lipophilicity but also on the extent of solvent drag during the course of the perfusion.