Pharmacokinetic and clinical equivalence of oral and intravenous ibandronate for metastatic bone disease

Abstract

While monthly infusions of intravenous (i.v.) bisphosphonates effectively reduce skeletal complications of metastatic bone disease, regular hospital visits are inconvenient for patients and may reduce their quality of life. Daily oral bisphosphonate therapy would allow long-term patient management in the community setting. However, the use of oral bisphosphonate therapy (e.g. oral clodronate) is limited in clinical practice, due to its relatively low efficacy in comparison with i.v. agents, poor gastrointestinal tolerability, and a large tablet size that is difficult for patients to administer. Ibandronate is a highly potent, third-generation aminobisphosphonate that has been developed in an oral formulation with a small, easy-to-swallow tablet and convenient once-daily dosing. Pharmacokinetic evaluations of oral ibandronate have shown a linear dose-dependent increase in plasma concentrations that is non-saturable, and is proportional to its effect on bone-resorption markers. This ensures predictability of response to a given oral dose of ibandronate, reducing safety concerns. Bioavailability analysis suggests that oral ibandronate (50 mg) taken once daily, 30 min before food, provides comparable bone-surface exposure to i.v. ibandronate (6 mg) infused every 3–4 weeks i.e. the two formulations are dose-equivalent. The clinical equivalence of oral ibandronate (50 mg) and i.v. ibandronate (6 mg) is indicated by comparable reductions in the relative risk of skeletal events in phase III trials of patients with bone metastases from breast cancer.