Renal handling of biphosphonate alendronate in rats

Bone tumor-homing nanotherapeutics for prolonged retention in tumor microenvironment and facilitated apoptotic process via mevalonate pathway inhibition

“…Notably, PLCSA-AD exhibited a 1.73-fold higher tumor disposition than PLCSA, which clearly indicates the enhanced bone tumor-homing ability conferred by AD decoration. Although PLCSA-AD showed slightly increased kidney accumulation compared to PLCSA ( p ​< ​0.05), this could be attributed to the bisphosphonate-specific transport mechanism in renal epithelial cells [ 38 , 39 ].

Fig.

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The Risk of Cumulative Renal Effects of Intravenous Bisphosphonates

“…Uptake and secretion from renal cells appear to be rate-determining and are controlled by unknown transport mechanisms that are selective for bisphosphonates. [49][50][51][52] Kino et al showed that when the plasma concentration increases, cellular influx of alendronate remains almost constant, whereas secretion from the cell is almost completely saturated. 49 This suggests that dose and peak plasma concentration affect the intracellular concentration of bisphosphonates and consequently the risk of cellular damage.…”

“…[49][50][51][52] Kino et al showed that when the plasma concentration increases, cellular influx of alendronate remains almost constant, whereas secretion from the cell is almost completely saturated. 49 This suggests that dose and peak plasma concentration affect the intracellular concentration of bisphosphonates and consequently the risk of cellular damage. This is most likely the reason why nephrotoxicity is not an issue for oral bisphosphonates, which are absorbed relatively slowly and are therefore administered as high daily doses compared with the lower monthly doses of I.V.…”

Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells

“…These compounds are not metabolized in either man or animal, and consequently, they are the active, parent compounds. The principal route of their elimination results from renal excretion [15] and these compounds can accumulate in the kidney during therapy [3] , [38] . It is important to note that potential nephrotoxicity has been observed in patients receiving high-dose bisphosphonate therapy, particularly when administrated by rapid intravenous administration [2] , [18] , [22] , [27] , [28] , [29] , [32] .…”