DETERMINATION OF TRANSPORT RATES FOR ARGININE AND ACETAMINOPHEN IN RABBIT INTESTINAL TISSUES IN-VITRO

The in vitro Ussing technique was employed to examine transport rates for acetaminophen and arginine across rabbit intestinal tissues. Manni tol and transepithelial: conductance were used to monitor the integrit y of rabbit intestinal tissues and the basal and stimulated short-circ uit current were measured to assess functional viability. Transepithel ial transport of acetaminophen, arginine, and mannitol was determined in rabbit jejunum, ileum, and distal colon. Transepithelial transport of arginine in the ileum and jejunum was composed of both passive (non saturable) (P-m = 0.06) and saturable components (K-T = 0.6-0.7 mM; J( max) = 0.3-0.4 mu mol/hr . cm(2)). The saturable component of arginine fluxes was abolished by pretreatment of the tissue with serosal ouaba in (0.1 mM). In the distal colon, both unidirectional arginine fluxes were nonsaturable. In the segments examined, both unidirectional fluxe s of acetaminophen were nonsaturable over the concentration range from 0.1 to 30 mM. These results provide values for maximal permeabilities attained by molecules traversing both the cellular and the paracellul ar pathways and, by comparison to their in vivo bioavailabilities, pro vide selection criteria for evaluating drug candidates for oral activi ty.