Ibandronate

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

Freely soluble

1.34e+01 g/L

Breast Feeding; Lactation; Bisphosphonates; Bone Density Conservation Agents; Diphosphonates

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

Warning

H302 (95.2%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 21 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The action of ibandronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting farnesyl pyrophosphate (FPP) synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

ibandronate

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

M - Musculo-skeletal system

QM - Musculo-skeletal system

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.

Ibanronate is not metabolized in humans.

No evidence of ibandronate being metabolized in humans. Route of Elimination: Ibandronate is eliminated by renal excretion. Unabsorbed ibandronate is eliminated unchanged in the feces. Half Life: 10-60 hours

UMD7G2653W

IBANDRONIC ACID

Established Pharmacologic Class [EPC] - Bisphosphonate

Chemical Structure [CS] - Diphosphonates

Ibandronic acid is a Bisphosphonate.

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.

Ibandronate is predominantly eliminated in the urine and the unabsorbed drug is eliminated unchanged in the feces.

The apparent terminal volume of distribution of ibandronate is 90-368L in headlthy subjects and 103L in postmenopausal women with osteopenia.

The total clearance of ibandronate is 84-160mL/min.

Use (kg; approx.) in Germany (2009): >100

For the treatment and prevention of osteoporosis in postmenopausal women.