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 (CL(R) approximately 60 mL/min). The CL(R) 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 approximately 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.
Roche Products Ltd., 40 Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AY, United Kingdom.
Joanne
J
Barrett
Eric
E
Worth
Frieder
F
Bauss
Solomon
S
Epstein
D001682:Biological Availability; D001711:Biotransformation; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000077557:Ibandronic Acid; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D010024:Osteoporosis / Q000188:drug therapy; D014018:Tissue Distribution
D004164:Diphosphonates; D000077557:Ibandronic Acid