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Pharmacotherapeutic Group: Bisphosphonate, for the treatment of bone diseases.
Alendronic acid is a bisphosphonate that acts as a specific inhibitor of osteoclast-mediated bone resorption. Bisphosphonates are synthetic analogs of pyrophosphate that binds to the hydroxyapatite found in bone.
Pharmacology: Pharmacodynamics: Alendronate sodium trihydrate is a bisphosphonate that inhibits osteoclastic bone resorption with no direct effect on bone formation. Preclinical studies have shown preferential localisation of alendronate to sites of active resorption. Activity of osteoclast is inhibited, but recruitment or attachment of osteoclasts is not affected. The bone formed during treatment with alendronate is of normal quality.
Treatment of Postmenopausal Osteoporosis: Osteoporosis is defined as bone mineral density (BMD) of the spine or hip 2.5 standard deviation (SD) below the mean value of a normal young population, or as a previous fragility fracture, irrespective of BMD.
The therapeutic equivalence of alendronate 70 mg once weekly (n=519) and alendronate 10 mg daily (n=370) was demonstrated in a 1-year multicentre study of postmenopausal women with osteoporosis. The mean increases from baseline in lumbar spine BMD at 1 year were 5.1% (95% CI: 4.8%, 5.4%) in the 70-mg once weekly group and 5.4% (95% CI: 5.1%, 5.8%) in the 10-mg daily group. The mean BMD increases were 2.3% and 2.9% at the femoral neck, 2.9% and 3.1% at the total hip in the 70-mg once weekly and 10-mg daily groups, respectively. The 2 treatment groups were also similar with regards to BMD increases at other skeletal sites.
Pharmacokinetics: Absorption and Bioavailability: Relative to an IV reference dose, the oral mean bioavailability of alendronate in women was 0.64% for doses ranging from 5-70 mg when administered after an overnight fast and 2 hrs before a standardized breakfast. Bioavailability was decreased similarly to an estimated 0.46% and 0.39% when alendronate was administered 1 hr or ½ hr before a standardized breakfast.
Distribution: Concentrations of drug in plasma following therapeutic oral doses are too low for analytical detection (<5 ng/mL). Protein-binding in human plasma is approximately 78%.
Metabolism and Elimination: Biotransformation: There is no evidence that alendronate is metabolized in animals or humans.
Elimination: The terminal half-life in humans is estimated to exceed 10 years, reflecting release of alendronate from the skeleton. Alendronate is not excreted through the acidic or basic transport systems of the kidney in rats; thus, it is not anticipated to interfere with the excretion of other medicinal products by those systems in humans.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity and carcinogenic potential.
