Effect of Lamivudine on Uptake of Organic Cations by Rat Renal Brush-Border and Basolateral Membrane Vesicles

Abstract

The effect of lamivudine on uptake of a representative organic cation, tetraethylammonium (TEA), by rat renal brush-border membrane vesicles (BBMV) and basolateral membrane vesicles (BLMV) has been investigated.The pH-driven uptake of TEA by BBMV (pHin = 60, pHout = 7.5) was inhibited by lamivudine. The IC50 value (concentration resulting in 50% inhibition) for the concentration-dependent effect of lamivudine on TEA uptake by BBMV after 30 s was 2668 μm whereas IC50 values for cimetidine and trimethoprim were <2.5 μm and < 25 μm, respectively. The early uptake of TEA by BLMV was also reduced significantly by lamivudine. The IC50 value for the concentration-dependent effect of lamivudine on uptake of TEA by BLMV at 30 s was > 25 mm, whereas the IC50 values for Cimetidine and trimethoprim were 2116 μm and 445 μm, respectively.These findings suggest that compared with other cationic drugs, such as trimethoprim and Cimetidine, lamivudine is a weak inhibitor of organic cation transport into the tubules by the brush-border and basolateral membranes of renal epithelial cells. It is unlikely lamivudine will have any significant effect on the excretion of co-administered cationic drugs by the renal tubules.