Fosamax.
FOSAMAXÂ
MSDÂ
Alendronate SodiumÂ
Bone Metabolism RegulatorÂ
Action And Clinical Pharmacology: Alendronate is an aminobisphosphonate that acts as a potent, specific inhibitor of osteoclast-mediated bone resorption. Bisphosphonates are synthetic analogs of pyrophosphate that bind to the hydroxyapatite found in bone.
Pharmacokinetics: Absorption: Relative to an i.v. reference dose, the mean oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and 2 hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women (0.78%) when administered after an overnight fast and 2 hours before breakfast. See Table I.   A study examining the effect of timing of a meal on the bioavailability of alendronate was performed in 49 postmenopausal women. Bioavailability was decreased (by approximately 40%) when 10 mg alendronate was administered either 0.5 or 1 hour before a standardized breakfast, when compared to dosing 2 hours before eating. In studies of treatment and prevention of osteoporosis, alendronate was effective when administered at least 30 minutes before breakfast.
Bioavailability was negligible whether alendronate was administered with or up to 2 hours after a standardized breakfast. Concomitant administration of alendronate with coffee or orange juice reduced bioavailability by approximately 60%.  Â
Distribution: Preclinical studies (in male rats) show that alendronate transiently distributes to soft tissues following 1 mg/kg i.v. 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
Metabolism: There is no evidence that alendronate is metabolized in animals or humans. Excretion: Following a single i.v. dose of 4 alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces. Following a single 10 mg i.v. dose, the renal clearance of alendronate was 71 mL/min, and systemic clearance did not exceed 200 mL/min. Plasma concentrations fell by more than 95% within 6 hours following i.v. administration. The terminal half-life in humans is estimated to exceed 10 years, probably reflecting release of alendronate from the skeleton. Based on the above, it is estimated that after 10 years of oral treatment with alendronate (10 mg daily) the amount of alendronate released daily from the skeleton is approximately 25% of that absorbed from the gastrointestinal tract.