Bisphosphonates pharmacokinetics

Mechanism of Action A bisphosphonate that inhibits normal and abnormal bone resorption, without retarding mineralization. Therapeutic Effect Leads to significantly increased bone mineral density reverses the progression of osteoporosis. Pharmacokinetics Poorly absorbed after oral administration. Protein binding 78%. After oral administration, rapidly taken into bone, with uptake greatest at sites of active bone turnover. Excreted in urine. Terminal half-life Greater than lOyr (reflects release from skeleton as bone is resorbed). 

Cremers SC, Pillai G, Papapoulos SE. Pharmacokinet-ics/pharmacodynamics of bisphosphonates use for optimisation of intermittent therapy for osteoporosis. Clin Pharmacokinet. 2005 44 551-570. 

A. Pharmacokinetics Pamidronate is administered intravenously. All of the other bisphosphonates are orally active, although less than ten percent of the administered dose is absorbed. Food significantly interferes with absorption. Bisphosphonates should be administered with six to eight ounces of water at least one hour before eating breakfast. The bisphosphonates are rapidly cleared from the plasma, primarily because they avidly bind to hydroxyapatite mineral of bone. Once bound to bone they are cleared over a period of months to years. Elimination from the body is solely through renal clearance, and the bisphosphonates should not be given to individuals with severe renal impairment. 

Cremers, S.C., Eekhoff, M.E., Den Hartigh, J., Hamdy, N.A., Vermeij, P., and Papapoulos, S.E. (2003). Relationships between pharmacokinetics and rate of bone turnover after intravenous bisphosphonate (olpadronate) in patients with Paget s disease of bone. J Bone Miner Res 18 868-875. 

Lasseter, K.C., Porras, A.G., Denker, A., Santhanagopal, A., and Daifotis, A. (2005). Pharmacokinetic considerations in determining the terminal elimination half-lives of bisphosphonates. Clin Drug Investig 25 107-114. 

Although the kidney has been identified as a major target organ for all bisphosphonates at the high doses used in preclinical toxicity studies, a clear therapeutic window still exists, enabhng bisphosphonates to be safely administered in general clinical use for the inhibition of bone resorption. However, there are differences in the therapeutic indices between individual agents and in their pharmacokinetic and pharmacodynamic profiles in patients with both normal and impaired renal function. 

Lin JFI. Bisphosphonates a review of their pharmacokinetic properties. Bone 1996 18 75-85. 

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