Pharmacokinetics of alendronate: an overview

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate, MK-217, Fosamax), an aminobisphosphonate, is a potent inhibitor of osteoclast-mediated bone resorption and is used for the treatment of bone disorders, osteoporosis and Pagets disease of bone. Alendronate, like all bisphosphonates, is absorbed poorly in animals and humans; oral bioavailability is less than 2% in all species studied, including humans. Systemically available alendronate disappears very rapidly from plasma, and the drug is either taken up by bone tissues or excreted by the kidneys. Renal excretion is the only route of elimination, and urinary recovery is similar among species, ranging from 30% to 50% in a 24-hour collection period. Studies in rats show that alendronate is actively secreted by an uncharacterised renal transport system, but not by anionic or cationic renal transport systems. Drug not excreted within 24 hours after dosing is believed to be sequestered in the skeleton, from which it is liberated slowly into the circulation to be eliminated renally. Once taken up by the bone, the elimination of alendronate from bone tissue is slow, ranging from 200 days in rats, 3 years in dogs and 12 years in humans. The phamacokinetics and unique targeting of alendronate to bone contribute to the utility of this drug for the management of skeletal disorders.