Ibandronate: A clinical pharmacological and pharmacokinetic update

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 (t(max) < 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 similar to60 mL/min). The CLR of ibandronate is linearly related to creatinine clearance. The sequestration of ibandronate in bone (V-D > 90 L) results in a multiphasic elimination (t(1/2) range similar to10-60 hours), characterized by the slow release of ibandronote from the bone compartment. The potency of ibandronote 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.