Impact of carriers in oral absorption: permeation across Caco-2 cells for the organic anions estrone-3-sulfate and glipizide

Gram L K, Rist G M, Lennernäs H, Steffansen B

Eur J Pharm Sci 2009 37(3-4): 378-386 

http://dx.doi.org/10.1016/j.ejps.2009.03.008

 

Carriers may mediate the permeation across enterocytes for drug substances being organic anions. Carrier mediated permeation for the organic anions estrone-3-sulfate (ES) and glipizide across Caco-2 cells were investigated kinetically, and interactions on involved carriers evaluated. Initial uptakes (PUP) at apical and basolateral membranes, apparent permeabilities (PAPP) and corresponding intracellular end-point accumulations (PEPA) of radioactive labeled compounds were studied. Possible effects of other anionic compounds were investigated. Apical PUP and absorptive PAPP for ES were inhibited and its absorptive PEPA prevented in presence of the investigated organic anions and apical PUP was saturable with Km 23 mM. Basolateral PUP and exsorptive PAPP were inhibited, its exsorptive PEPA was prevented, and basolateral PUP and exsorptive PAPP were saturable with Km 44 mM and 38 mM, respectively. BCRP inhibition affected both absorptive an exsorptive PEPA and PAPP for ES. Glipizide apical PUP and absorptive PAPP were not inhibitable. Basolateral PUP for glipizide was inhibitable, its PEPA prevented, and PUP was saturable wit