Zoledronic acid

272.09

272.09

1806241-263-5

70HZ18PH24

721517

DTXSID0042668

C80120

M05BA08|M - Musculo-skeletal system

2933399090

153

-4.3

Solid

2.13±0.1 g/cm3(Predicted)

237-240 °C

764.0±70.0 °C(Predicted)

415.8±35.7 °C

1.719

Sparingly soluble with water.

1.53E-24mmHg at 25°C

21/22-36/37/38

24/25-36/37/39

Xi

Patients experiencing an overdose may present with renal impairment, hypocalcemia, hypophosphatemia, and hypomagnesemia. Overdose should be managed through intravenous administration of the insufficient ions.

Zoledronic acid is 23-53% protein bound in plasma.

Zoledronic acid is indicated to treat hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, osteoporosis in men and postmenopausal women, glucocorticoid induced osteoporosis, and Paget's disease of bone in men and women. Zoledronic acid is also indicated for the prevention of osteoporosis in post menopausal women and glucocorticoid induced osteoporosis.|Prevention of skeletal-related events and treatment of tumour-induced hypercalcaemia.|Prevention of skeletal-related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in adult patients with advanced malignancies involving bone., , Treatment of adult patients with tumour-induced hypercalcaemia. ,|4 mg / 5 ml and 4 mg / 100 ml:Prevention of skeletal-related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in adult patients with advanced malignancies involving bone.Treatment of adult patients with tumour-induced hypercalcaemia (TIH).5 mg / 100 ml:Treatment of osteoporosis:in post-menopausal women;in men;at increased risk of fracture, including those with a recent low-trauma hip fracture.Treatment of osteoporosis associated with long-term systemic glucocorticoid therapy:in post-menopausal women;in men;at increased risk of fracture.Treatment of Paget's disease of the bone in adults.|Prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in adult patients with advanced malignancies involving bone.Treatment of adult patients with tumour-induced hypercalcaemia (TIH).|Prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in adult patients with advanced malignancies involving bone;treatment of adult patients with tumour-induced hypercalcaemia (TIH).|Treatment of osteoporosis:in post-menopausal women;in men;at increased risk of fracture, including those with a recent low-trauma hip fracture.Treatment of osteoporosis associated with long-term systemic glucocorticoid therapy in post-menopausal women and in men at increased risk of fracture.Treatment of Paget's disease of the bone.|Treatment of osteoporosis:, , , in post-menopausal women;, in men;, , , at increased risk of fracture including those with a recent low-trauma hip fracture., , Treatment of osteoporosis associated with long-term systemic glucocorticoid therapy:, , , in post-menopausal women;, in men;, , , at increased risk of fracture., , Treatment of Paget's disease of the bone in adults.,|Prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in patients with advanced malignancies involving bone;treatment of tumour-induced hypercalcaemia (TIH);prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in patients with advanced malignancies involving bone;treatment of tumour-induced hypercalcaemia (TIH);prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in adult patients with advanced malignancies involving bone;treatment of adult patients with tumour-induced hypercalcaemia (TIH).|Treatment of osteoporosisin post-menopausal womenin adult menat increased risk of fracture, including those with recent low-trauma hip fracture.Treatment of osteoporosis associated with long-term systemic glucocorticoid therapyin post-menopausal womenin adult menat increased risk of fracture.Treatment of Paget's disease of the bone in adults.|Osteogenesis imperfecta, Prevention of fracture and bone loss in postmenopausal women with early-stage breast cancer treated with aromatase inhibitors, Prevention of skeletal related events in patients with advanced malignancies involving bone, Tumour-induced hypercalcaemia|Treatment of osteoporosis, Treatment of Paget’s disease of the bone|Drug: Zoledronicacid

Zoledronic acid is a third generation, nitrogen containing bisphosphonate that inhibits osteoclast function and prevents bone resorption. The therapeutic window is wide as patients are unlikely to suffer severe effects from overdoses and the duration of action is long. Patients should be counselled regarding the risk of electrolyte deficiencies, renal impairment, osteonecrosis of the jaw, atypical femoral fractures, bronchoconstriction, hepatic impairment, hypocalcemia, and embryo-fetal toxicity.

Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS. (See all compounds classified as Bone Density Conservation Agents.)

A 4mg intravenous dose reaches a C_max of 370±78.5ng/mL, with a T_max of 0.317±0.014h, and an AUC of 788±181ng\*h/mL. A 5mg intravenous dose reaches a C_max of 471±76.1ng/mL, with a T_max of 0.368±0.005h, and an AUC of 917±226ng\*h/mL.|Zoledronic acid is 39 ± 16% eliminated in the urine as the unmetabolized parent drug.|Zoledronic acid has a renal clearance of 3.7 ± 2.0 L/h.

Zoledronic acid is not metabolized _in vivio_.

Zoledronic acid has a terminal elimination half life of 146 hours.

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. Etidronic acid also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption. Nitrogen containing bisphosphonates such as zoledronate 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. zoledronate also activated caspases which further contribute to apoptosis.

2-(imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonic acid

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