Loron - General Information
A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. [PubChem]
Pharmacology of Loron
Loron is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and tiludronate. Loron affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the clodronate that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The remainder has a very high affinity for bone tissue, and is rapidly absorbed onto the bone surface. Loron has been shown to prevent or delay skeletal-related events and decrease bone pain as well as normalize calcium levels in the presence of hypercalcemia.
Additional information about Loron
Loron Indication: For the management of hypercalcemia of malignancy and as an adjunct in the management of osteolysis resulting from bone metastases of malignant tumors.
Mechanism Of Action: The bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. The exact mechanism of action of clodronate is not known, however it is known that it does not inhibit protein isoprenylation but can be metabolized intracellularly to a β-γ-methylene (AppCp-type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Inhibition of the ADP/ATP translocase by the metabolite AppCCl2p is a likely route by which clodronate causes osteoclast apoptosis and inhibits bone resorption. Recently, the slime mold Dictyostelium discoideum was shown to take up bisphosphonates by pinocytosis. In these cells, clodronate, but not other pharmacologically active bisphosphonates, was incorporated into adenine nucleotides, which could potentially explain why this bisphosphonate sometimes seems to act differently than the other bisphosphonates. Loron, like all biphosphonates, also binds protein-tyrosine-phosphatase.
Drug Interactions: Aluminium Formation of non-absorbable complexes
Bismuth Formation of non-absorbable complexes
Calcium Formation of non-absorbable complexes
Dihydroxyaluminium Formation of non-absorbable complexes
Estramustine Increases the levels of estramustine
Magnesium oxide Formation of non-absorbable complexes
Magnesium Formation of non-absorbable complexes
Sucralfate Formation of non-absorbable complexes
Iron Formation of non-absorbable complexes
Food Interactions: Decreases absorption, take on an empty stomach.
Generic Name: Clodronate
Synonyms: Not Available
Drug Category: Antihypocalcemic Agents; Bisphosphonates; Osteoporosis Prophylactic; Antineoplastic Agents
Drug Type: Small Molecule; Approved
Absorption: After oral administration, absorption is estimated at 1–3% of the ingested dose because of the low uptake from the gastrointestinal tract.
Toxicity (Overdose): Decreases in serum calcium following substantial overdosage may be expected in some patients. Signs and symptoms of hypocalcemia also may occur in some of these patients.
Protein Binding: 2%-36%
Biotransformation: Clodronate is not metabolized in humans.
Half Life: Approximately 13 hours.
Dosage Forms of Loron: Solution Intravenous
Chemical IUPAC Name: (dichloro-phosphonomethyl)phosphonic acid
Chemical Formula: CH4Cl2O6P2
Clodronate on Wikipedia: https://en.wikipedia.org/wiki/Clodronate
Organisms Affected: Humans and other mammals