β‐Cyclodextrin Reduces Bioavailability of Orally Administered [3H]Benzo[a]pyrene in the Rat

The excretion and plasma kinetics of total radioactivity were studied following single oral administration of [3H]benzo[a]pyrene after multiple oral administration of β‐cyclodextrin at 0, 5, 50, or 500 mg/kg/day. The AUC and Cmax values in male and female rats following administration of [3H]benzo[a]pyrene in combination with 5 to 500 mg/kg β‐cyclodextrin were considerably lower than that in rats administered [3H]benzo[a]pyrene alone. At all dose levels of β‐cyclodextrin, the excretion of total radioactivity was almost entirely via feces, with <2% recovered in urine, demonstrating either that absorption of the orally administered dose was low or that, for any absorbed material, biliary excretion was the main route of excretion. However, following administration of vehicle, up to 5% of the administered radioactivity was recovered in the urine, suggesting that absorption may have been reduced by the presence of β‐cyclodextrin in the intestine. At all dose levels of β‐cyclodextrin, there was minimal retention of radioactivity in the carcase at the end of the collection period. β‐Cyclodextrin did not affect the apparent terminal half‐life of radioactivity. Therefore, the reduced systemic exposure of rats to radioactivity in the presence of β‐cyclodextrin is likely related to a reduced oral bioavailability. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:114-119, 2005