Tiludronate

318.61 g/mol

318.61

618-322-0

6PNS59HP4Y

DTXSID10237966

M - Musculo-skeletal system

140 Ų

-0.6

174-177 °C

6.97e+00 g/L

Patients experiencing an overdose may present with hypocalcemia. Patients given doses of 6mg/kg/day for 2 days have experienced acute renal failure and death. Treat overdose with symptomatic and supportive care. Dialysis will not be useful for removal of the drug from serum.

Tiludronic acid is approximately 90% protein bound in serum. It is mostly bound to albumin.

Tiludronic acid is indicated to treat Paget's disease of bone in patients with serum alkaline phosphatase levels ≥2 times the upper limit of normal, with symptoms, or with risk of future complications.

Tiludronic acid is a bisphosphonate that prevents osteoclasts from resorbing bone. The duration of action is quite long due to the slow clearance from the bone, and the therapeutic window is wide. Patients should be counselled regarding the risk of upper GI mucosal irritation as well as gastric and duodenal ulcers.

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 single 400mg dose of tiludronic acid reaches a C_max of 3.35±1.07mg/L, with a T_max of 1.7—0.9h, and and AUC of 27.2±9.0mg\*h/L. Tiludronic acid has an oral bioavailability of 2-11% with an average of 6%.|Tiludronic acid is 60% eliminated in the urine as the unchanged parent drug.|The volume of distribution of tiludronic acid is estimated to be between 30L and 60L. Due to the unknown clearance rate from bone, this may underestimate the true volume of distribution.|Tiludronic acid has a renal clearance of 0.68L/h in healthy subjects and 0.47L/h in subjects with Paget's disease. Approximately 50% of tilurdronic acid binds to bone but the rate of clearance from the bone is unknown.

Tiludronic acid is not metabolized _in vitro_ in human liver microsomes.

The mean plasma elimination half-life is 150 hours, though the elimination rate from bone is unknown. The terminal phase half life is approximately 40h after a single IV dose of 10-30mg.

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. Tiludronate inhibits protein-tyrosine-phosphatase, which increases tyrosine phosphorylation, and disrupts podosome formation. Tiludronic 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.

(4-chlorophenyl)thiomethylene bisphosphonic acid

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients