Acidum Clodronicum
Acidum Clodronicum Uses, Dosage, Side Effects, Food Interaction and all others data.
Acidum Clodronicum 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.
Acidum Clodronicum is not FDA approved, but is approved in Canada.
Acidum Clodronicum 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 | Acidum Clodronicum |
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 |
Uses
Acidum Clodronicum is a bisphosphonate used to treat osteoporosis in postmenopausal women, hypercalcemia of malignancy, and osteolysis.
Acidum Clodronicum is indicated as an adjunct in the management of osteolysis from bone metastases of malignant tumors and for management of hypercalcemia of malignancy.
Acidum Clodronicum is also used to associated treatment for these conditions: Hypercalcemia of Malignancy, Osteolytic Bone metastases
How Acidum Clodronicum 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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