In-vitro potencies of histamine H2-receptor antagonists on tetraethylammonium uptake in rat renal brush-border membrane vesicles

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Abstract
The histamine H2 antagonists cimetidine, ranitidine and famotidine are organic bases that are cleared from the body by active renal tubular secretion involving the organic cation transporter in the proximal tubule. To determine the potential for competition for the transporter between these drugs and other drugs, their inhibitory potencies were assessed in-vitro, using rat renal brush-border membrane vesicles and tetraethylammonium as the substrate. The concentration-dependent effect of cimetidine, ranitidine and famotidine on the 15-s proton-stimulated uptake of tetraethylammonium into the membrane vesicles was studied using five different rat kidneys. The order of inhibition potencies was: cimetidine (mean IC50= 1·07 μm) > famotidine (2·43 μm) > ranitidine (55·4 μm). The results indicate the potential for drug interactions in the kidney, especially for cimetidine and famotidine.