Studies of the oral bioavailability of alendronate*

Abstract

Clinical studies were performed to examine the oral bioavailability of alendronate (4-amino-1-hydroxy-butylidene-1,1-bisphosphonate monosodium). All studies, with the exception of one performed in men, involved postmenopausal women. Short-term (24 to 36 hours) urinary recovery of alendronate after an intravenous dose of 125 to 250 micrograms averaged about 40% in both men and women. In women, oral bioavailability of alendronate was independent of dose (5 to 80 mg) and averaged (90% confidence interval) 0.76% (0.58, 0.98) when taken with water in the fasting state, followed by a meal 2 hours later. Bioavailability was similar in men [0.59%, (0.43, 0.81)]. Taking alendronate either 60 or 30 minutes before a standardized breakfast reduced bioavailability by 40% relative to the 2-hour wait. Taking alendronate either concurrently with or 2 hours after breakfast drastically (> 85%) impaired availability. Black coffee or orange juice alone, when taken with the drug, also reduced bioavailability (approximately 60%). Increasing gastric pH, by infusion of ranitidine, was associated with a doubling of alendronate bioavailability. A practical dosing recommendation, derived from these findings and reflective of the long-term nature of therapy for a disease such as osteoporosis, is that patients take the drug with water after an overnight fast and at least 30 minutes before any other food or beverage.

Bisphosphonates: therapeutics potential and recent advances in drug delivery

“…(Tanvetyanon & Stiff, 2006). But majority of cases have been reversible (Gertz et al, 1995;Osteoporosis, 2013). Novel drug delivery system (DDS) approaches can be undertaken to overcome the shortcoming of BPs, thus making them more patient compliant (De Groen et al, 1996;Giger et al, 2013).…”

A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D3 in breast cancer patients with bone metastases

“…If suppression was maximal, then neither telopeptide levels nor pain scores would be expected to change as a result of a high dose of vitamin D. It should be emphasized that patients in this study were administered different bisphosphonates, and these were given both orally and intravenously. As the bioavailability of oral bisphosphonates is highly variable, 36 it could be argued that this may impact on the results of the study. However, the authors believe that the cumulative doses of bisphosphonates administered in the oncology setting are so high that differences in bioavailability are not likely to be significant in these cases.…”

Bisphosphonates in the treatment of metabolic bone diseases

“…What does not bind to bone is excreted in the urine unchanged (6,7). Bisphosphonates are poorly absorbed by the gut, with less than 1% bioavailability after oral administration (8). This poor absorption is related to the heavy negative charge of the bisphosphonate molecule, which makes transport across lipophilic cell membranes difficult.…”