Aldren 70 Mechanism of Action

Pharmacology: Mechanism of Action: Alendronic acid (Aldren 70) is a bisphosphonate that binds to bone hydroxyapatite and specifically inhibits the activity of osteoclasts, the bone-resorbing cells. Alendronate sodium reduces bone resorption with no direct effect on bone formation. Histomorphometry in baboons and rats showed that alendronate sodium treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass.
Pharmacokinetics: Relative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate sodium in women was 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and two hours before a standardized breakfast. Bioavailability was decreased (by approximately 40%) when 10 mg alendronate sodium was administered either 0.5 or 1 hour before a standardized breakfast, when compared to dosing 2 hours before eating. Bioavailability was negligible whether alendronate sodium was administered with or up to two hours after a standardized breakfast. Alendronate sodium transiently distributes to soft tissues following 1 mg/kg IV administration but is then rapidly redistributed to bone or excreted in the urine. The mean steady-state volume of distribution, exclusive of bone, is at least 28 L in humans. Protein binding in human plasma is approximately 78%. There is no evidence that alendronate sodium is metabolized in animals or humans. Following a single IV dose of [¹⁴C] alendronate sodium, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces. The terminal half-life in humans is estimated to exceed 10 years, probably reflecting release of alendronate sodium from the skeleton.