IN-VITRO POTENCIES OF HISTAMINE H-2-RECEPTOR ANTAGONISTS ON TETRAETHYLAMMONIUM UPTAKE IN RAT RENAL BRUSH-BORDER MEMBRANE-VESICLES

The histamine H-2 antagonists cimetidine, ranitidine and famotidine ar e organic bases that are cleared from the body by active renal tubular secretion involving the organic cation transporter in the proximal tu bule. To determine the potential for competition for the transporter b etween these drugs and other drugs, their inhibitory potencies were as sessed in-vitro, using rat renal brush-border membrane vesicles and te traethylammonium 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 u sing five different rat kidneys. The order of inhibition potencies was : cimetidine (mean IC50 = 1.07 muM) > famotidine (2.43 muM) > ranitidi ne (55.4 muM). The results indicate the potential for drug interaction s in the kidney, especially for cimetidine and famotidine.