Sindronat

Sindronat Uses, Dosage, Side Effects, Food Interaction and all others data.

Sindronat is a first generation bisphosphonate similar to etidronic acid and tiludronic acid. These drugs were developed to mimic the action of pyrophosphate, a regulator of calcification and decalcification. clodronate’s use has decreased over the years in favor of the third generation, nitrogen containing bisphosphonate zoledronic acid, ibandronic acid, minodronic acid, and risedronic acid.

Sindronat is not FDA approved, but is approved in Canada.

Sindronat is a first generation bisphosphonate that inhibits osteoclast mediated bone resorption. It has a wide therapeutic index as a large overdose is required for significant toxicity and a long duration of action due to the slow release from bone. Patients should be counselled regarding the risk of hypocalcemia, hypovolemia, renal insufficiency, transient hyperphosphatemia, and transient hyperparathyroidism.

Trade Name Sindronat
Generic Clodronic acid
Clodronic acid Other Names Acide clodronique, Acido clodronico, Acidum clodronicum, Clodronate, Clodronic acid, Clodronsaeure, Clodronsäure, Dichloromethylidene diphosphonate
Type
Formula CH4Cl2O6P2
Weight Average: 244.892
Monoisotopic: 243.886016298
Protein binding

Clodronic acid is 36% protein bound in plasma.

Groups Approved, Investigational, Vet approved
Therapeutic Class
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Sindronat
Sindronat

Uses

Sindronat is a bisphosphonate used to treat osteoporosis in postmenopausal women, hypercalcemia of malignancy, and osteolysis.

Sindronat is indicated as an adjunct in the management of osteolysis from bone metastases of malignant tumors and for management of hypercalcemia of malignancy.

Sindronat is also used to associated treatment for these conditions: Hypercalcemia of Malignancy, Osteolytic Bone metastases

How Sindronat works

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.

First generation bisphosphonates closely mimic the structure of pyrophosphate, which can be incorporated into ATP anologues that cannot be hydrolyzed, disrupting all ATP mediated actions of osteoclasts.

Toxicity

Patients experiencing an overdose may present with hypocalcemia, while severe overdoses can present with kidney failure, liver damage, and unconsciousness. Overdose can be managed through symptomatic and supportive care, including monitoring and administration of electrolytes including calcium. Gastric lavage may remove unabsorbed drug in the gastrointestinal tract.

Food Interaction

  • Take on an empty stomach. Co-administration with food may decrease absorption.

Elimination Route

Oral clodronic acid has a bioavailability of 1-2%. A 200mg intravenous dose reaches a Cmax of 16.1mg/L with an AUC of 44.2mg*h/L. A 200mg intramuscular dose reaches a Cmax of 12.8mg/L with an AUC of 47.5mg*h/L. Further pharmacokinetic data for clodronic acid are not readily available.

Half Life

The mean plasma half life of clodronate is 5.6h.

Clearance

The renal clearance of clodronate is approximately 90mL/min.

Elimination Route

Clodronate is eliminated unchanged in the urine.

Innovators Monograph

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*** Taking medicines without doctor's advice can cause long-term problems.
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