Pharmacokinetics of intravenous alendronate

Alendronate is a potent bisphosphonate that has been studied for the treatm ent of osteoporosis and Paget's disease of the bone. To examine the pharmac okinetics of this drug, several groups of postmenopausal women were dosed i ntravenously in several studies. Twelve patients with metastatic bone disea se were administered an intravenous dose of 10 mg of C-14-labeled alendrona te (similar to 26 mu Ci), and plasma, feces, and urine samples were collect ed for 72 hours. Radioactivity was excreted almost exclusively in urine, an d all of it was accounted for by alendronate. Overall recovery accounted fo r 47% of dose, with the remainder presumed to be retained in bone. Metaboli sm of alendronate was not observed. Renal clearance of alendronate was 71 m L/min. An additional 10 subjects were given repeated IV administrations of alendronate to demonstrate that previous exposure does not alter the pharma cokinetic behavior of the drug. Examination of the findings from these and other studies in which alendronate was administered intravenously revealed that disposition of single doses is linear ill the range of 0.125 to 10 mg, With the possible exception of a somewhat greater skeletal retention of a systemically administered dose, the pharmacokinetics of IV alendronate were found to be similar to those of other bisphosphonates. (C) 1999 the Americ an College of Clinical Pharmacology.