CLODRONIC ACID

Absorption

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.

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.

The Uses of CLODRONIC ACID

Clodronic Acid is a bisphosphonate that can be used in the treatment of osteoporosis. Its ATP-analogs can inhibit cell signaling pathways.

Indications

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

Background

Clodronic acid 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.
Clodronic acid is not FDA approved, but is approved in Canada.

Pharmacokinetics

Clodronic acid 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.

Metabolism

Clodronate is not metabolized in humans.