Pharmacokinetics of alendronate: An overview

Alendronate (4-amino-1-hydroxybutylidene-1, 1-bisphosphonate, MK-217, Fosam ax), an aminobisphosphonate, is a potent inhibitor of osteoclast-mediated b one resorption and is used for the treatment of bone disorders, osteoporosi s and Paget's disease of bone. Alendronate, like all bisphosphonates, is ab sorbed poorly in animals and humans; oral bioavailability is less than 2% i n all species studied, including humans. Systemically available alendronate disappears very rapidly from plasma, and the drug is either taken up by bo ne tissues or excreted by the kidneys. Renal excretion is the only route of elimination, and urinary recovery is similar among species, ranging from 3 0% to 50% in a 24-hour collection period. Studies in rats show that alendro nate is actively secreted by an uncharacterised renal transport system, but not by anionic or cationic renal transport systems. Drug not excreted with in 24 hours after dosing is believed to be sequestered in the skeleton, fro m which if is liberated slowly into the circulation to be eliminated renall y Once taken up by the bone, the elimination of alendronate from bone tissu e is slow, ranging from 200 days in mts, 3 years in dogs and 12 years in hu mans. The pharmacokinetics and unique targeting of alendronate to bone cont ribute to the utility of this drug for the management of skeletal disorders .