Renal handling of biphosphonate alendronate in rats

Alendronate is a bisphosphonate that is secreted via a saturable pathway in rat kidney. This study is designed to discover if the rate-determining step in its net renal secretion is uptake into the renal tubule. The tissue uptake clearance of alendronate by the kidney, estimated from an integration plot analysis and normalized with respect to plasma protein binding, was 4.2 times higher at a tracer dose than that of inulin, indicating uptake of alendronate by the renal tubules. The uptake clearance is comparable with the net secretion clearance obtained from an infusion study, indicating that the rate-determining step in the net secretion is uptake under the tracer conditions. When the dose was increased, however, there was no reduction in uptake clearance while the net secretion clearance fell to almost zero. The urinary excretion clearance defined with respect to the steady state concentration in the kidney also fell to almost zero. This result suggests that saturation of the net secretion of alendronate is caused by saturation of membrane transport through the brush-border membrane. Thus, it would seem that there is a transport mechanism for alendronate on the brush-border membrane of kidney epithelial cells.