Pamidronate (sodium salt)

Pamidronate is an amino bisphosphonate that inhibits farnesyl pyrophosphate (FPP) synthase (IC₅₀s = 0.85 and 0.20 µM in J774 cells and for human recombinant FPP synthase, respectively).¹ In rats, it inhibits bone resorption when used at doses of 16 µmol/kg per day, impairs long bone growth at ≥40 µmol/kg per day, and has anti-hypercalcemic effects in a rat hypercalcemia model.^2,3 At high concentrations, pamidronate induces activation of matrix metalloproteinase-2 (MMP-2), NF-κB, and caspase-3, leading to cell death, which can be prevented by activated protein C.⁴ Formulations containing pamidronate have been used to treat hypercalcemia, Paget’s disease, metastatic bone disease, and multiple myeloma.

WARNING This product is not for human or veterinary use.

1. Dunford, J.E., Thompson, K., Coxon, F.P., et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J. Pharmacol. Exp. Ther. 296(2), 235-242 (2001).

2. Reitsma, P.H., Bijovet, O.L.M., Verlinden-Ooms, H., et al. Kinetic studies of bone and mineral metabolism during treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in rats. Calcif. Tissue Int. 32(2), 145-157 (1980).

3. Okada, M., Noguchi, S., Hasegawa, Y., et al. Effect of pamidronate in a rat hypercalcemia model induced by cholecalciferol. Arzneimittelforschung 42(4), 543-546 (1992).

4. Seol, J.-W., Lee, Y.-J., Jackson, C.J., et al. Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways. Int. J. Mol. Med. 27(6), 835-840 (2011).