PT  - JOURNAL ARTICLE
AU  - Lee, Kiho
AU  - Ng, Chee
AU  - Brouwer, Kim L. R.
AU  - Thakker, Dhiren R.
TI  - Secretory Transport of Ranitidine and Famotidine across Caco-2 Cell Monolayers
AID  - 10.1124/jpet.102.038521
DP  - 2002 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 574--580
VI  - 303
IP  - 2
4099  - http://jpet.aspetjournals.org/content/303/2/574.short
4100  - http://jpet.aspetjournals.org/content/303/2/574.full
SO  - J Pharmacol Exp Ther2002 Nov 01; 303
AB  - The secretory transport of the H2-antagonists, ranitidine and famotidine, across Caco-2 cell monolayers was found to be a saturable process. Both drugs exhibited greater permeability in the basolateral (BL) to apical (AP) direction than in the AP to BL direction, indicating apically directed secretion; BL to AP transport was inhibited by P-glycoprotein (P-gp) inhibitors verapamil and cyclosporin A. The cellular uptake of ranitidine across the BL membrane was saturable and temperature dependent, indicative of carrier-mediated transport. The Km andVmax for the uptake process were estimated to be 66.9 mM and 20.9 nmol/mg of protein/min, respectively. The uptake of [14C]ranitidine across the BL membrane was inhibited by unlabeled ranitidine and structurally diverse organic cations. The tetraethylammonium (TEA)-sensitive organic cation transporters are not involved in the uptake of ranitidine and famotidine across the BL membrane of Caco-2. This conclusion was based on the evidence that functionally active TEA-sensitive organic cation transporters did not exist in the BL membranes of the Caco-2 cells, whereas the functionally active TEA-sensitive organic cation transporter(s) in LLC-PK1 cells did not contribute to the transport of ranitidine or famotidine across the cell monolayers. Thus, we conclude that the secretory transport of ranitidine and famotidine across Caco-2 cell monolayers is mediated by 1) a carrier in the BL membrane that is distinct from the TEA-sensitive organic cation transporter(s) and 2) P-gp in the apical membrane. The American Society for Pharmacology and Experimental Therapeutics