イバンドロネート

Freely soluble

1.34e+01 g/L

Ibandronate is a nitrogen containing bisphosphonate used to treat and prevent osteoporosis in postmenopausal women. The therapeutic index is wide as overdoses are not especially toxic, and the duration of action is long as the half life can be up to 157 hours. Patients should be counselled regarding the risk of upper GI adverse reactions, hypocalcemia, musculoskeletal pain, osteonecrosis of the jaw, atypical fractures of the femur, and severe renal impairment.

Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act. Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption. Nitrogen containing bisphosphonates such as ibandronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. ibandronate also activated caspase-3 which contribute to apoptosis.

Oral ibandronate is 0.63% bioavailable. In a study of healthy males, a 10mg oral dose had a Tmax of 1.1±0.6h and a Cmax of 4.1±2.6ng/mL. The Tmax is approximately 1 hour, while Cmax varies depending on dose. A 2mg intravenous dose of ibandronate has an AUC of 316ng\*h/mL, a 4mg intravenous dose of ibandronate has an AUC of 581ng\*h/mL, and a 6mg intravenous dose of ibandronate has an AUC of 908ng\*h/mL.