STUDIES OF THE ORAL BIOAVAILABILITY OF ALENDRONATE

Clinical studies were performed to examine the oral bioavailability of alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate monosodiu m). 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 mu g averaged abou t 40% in both men and women. In women, oral bioavailability of alendro nate 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 sta te, followed by a meal 2 hours later. Bioavailability was similar in m en [0.59%, (0.43, 0.81)]. Taking alendronate either 60 or 30 minutes b efore 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 b ioavailability (approximately 60%), Increasing gastric pH, by infusion of ranitidine, was associated with a doubling of alendronate bioavail ability. A practical dosing recommendation, derived from these finding s 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 o vernight fast and at least 30 minutes before any other food or beverag e.