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THERAPEUTIC REVIEW |
From Roche Products Ltd., Welwyn Garden City, Hertfordshire, United Kingdom (Dr. Barrett, Mr. Worth); Pharma Research Penzberg, Roche Diagnostics GmbH, Penzberg, Germany (Dr. Bauss); Institute of Pharmacology and Toxicology, Heidlberg University, Mannheim, Germany (Dr. Bauss); and Mount Sinai School of Medicine, Mount Sinai Medical Center, New York (Dr. Epstein).
Ibandronate is a potent nitrogen-containing bisphosphonate. It has a strong affinity for bone mineral and potently inhibits osteoclast-mediated bone resorption. Ibandronate is effective for the treatment of hypercalcemia of malignancy, metastatic bone disease, postmenopausal osteoporosis, corticosteroid-induced osteoporosis, and Paget's disease. Oral ibandronate is rapidly absorbed (tmax < 1 hour), with a low bioavailability (0.63%) that is further reduced (by up to 90%) in the presence of food. Ibandronate has a wide therapeutic index and is not metabolized and, therefore, has a low potential for drug interactions. Given its metabolic stability, ibandronate is eliminated from the blood by partitioning into bone (40%-50%) and through renal clearance (CLR 
60 mL/min). The CLR of ibandronate is linearly related to creatinine clearance. The sequestration of ibandronate in bone (VD > 90 L) results in a multiphasic elimination (t
range 10-60 hours), characterized by the slow release of ibandronate from the bone compartment. The potency of ibandronate and its sequestration into bone allow ibandronate to be developed as oral and intravenous injection formulations that can be administered with convenient extended between-dose intervals.
Key Words: Ibandronate • pharmacokinetics • pharmacy-dynamics • bisphosphonates • postmenopausal osteoporosis • drug interactions • tolerability
Address for reprints: Joanne Barrett, PhD, Roche Products Ltd., 40 Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AY, United Kingdom.
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