Skelid
Skelid - General Information
Skelid is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates.
Pharmacology of Skelid
Skelid is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and clodronate. Skelid affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the tiludronate 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.
Skelid for patients
Patients receiving SKELID should be instructed to:
- Take SKELID with 6 to 8 ounces of plain water.
- SKELID should not be taken within 2 hours of food.
- Maintain adequate vitamin D and calcium intake.
- Calcium supplements, aspirin, and indomethacin should not be taken within 2 hours before or 2 hours after SKELID.
- Aluminum- or magnesium-containing antacids, if needed, should be taken at least 2 hours after taking SKELID.
Skelid Interactions
The bioavailability of SKELID is decreased 80% by calcium, when calcium and SKELID are administered at the same time, and 60% by some aluminum- or magnesium-containing antacids, when administered 1 hour before SKELID. Aspirin may decrease bioavailability of SKELID by up to 50% when taken 2 hours after SKELID. The bioavailability of SKELID is increased 2-4 fold by indomethacin but is not significantly altered by coadministration of diclofenac. The pharmacokinetic parameters of digoxin are not significantly modified by SKELID coadministration. In vitro studies show that tiludronate does not displace warfarin from its binding site on protein.
Skelid Contraindications
SKELID is contraindicated in individuals with known hypersensitivity to any component of this product.
Additional information about Skelid
Skelid Indication: For treatment of Paget's disease of bone (osteitis deformans).
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. In vitro studies indicate that tiludronate acts primarily on bone through a mechanism that involves inhibition of osteoclastic activity with a probable reduction in the enzymatic and transport processes that lead to resorption of the mineralized matrix. Bone resorption occurs following recruitment, activation, and polarization of osteoclasts. Skelid appears to inhibit osteoclasts by at least two mechanisms: disruption of the cytoskeletal ring structure, possibly by inhibition of protein-tyrosine-phosphatase, thus leading to detachment of osteoclasts from the bone surface and the inhibition of the osteoclastic proton pump.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Tiludronate
Synonyms: Acide tiludronique [INN-French]; Acido tiludronico [INN-Spanish]; Acidum tiludronicum [INN-Latin]; Tiludronate disodium; Tiludronic acid; Tiludronic Acid Disodium Salt
Drug Category: Antihypocalcemic Agents; Osteoporosis Prophylactic
Drug Type: Small Molecule; Approved
Other Brand Names containing Tiludronate: Skelid;
Absorption: The mean oral bioavailability in healthy male subjects is 6% after an oral dose equivalent to 400 mg tiludronic acid administered after an overnight fast and 4 hours before a standard breakfast. In single-dose studies, bioavailability was reduced by 90% when an oral dose equivalent to 400 mg tiludronic acid was administered with, or 2 hours after, a standard breakfast compared to the same dose administered after an overnight fast and 4 hours before a standard breakfast.
Toxicity (Overdose): Based on the known action of tiludronate, hypocalcemia is a potential consequence of overdose. In one patient with hypercalcemia of malignancy, intravenous administration of high doses (800 mg/day total dose, 6 mg/kg/day for 2 days) was associated with acute renal failure and death.
Protein Binding: Approximately 90% bound to human serum protein (mainly albumin) at plasma concentrations between 1 and 10 mg/L.
Biotransformation: In vitro, tiludronic acid is not metabolized in human liver microsomes and hepatocytes. There is no evidence that tiludronate is metabolized in humans.
Half Life: Half-life in healthy subjects is 50 hours following administration of a 400 mg single oral dose. Half-life in pagetic patients is about 150 hours following administration of 400 mg tiludronate a day for 12 days. In patients with renal insufficiency (creatinine clearance between 11 and 18 mL per minute [mL/min]), half-life is 205 hours from plasma after administration of a single, oral dose equivalent to 400 mg tiludronate.
Dosage Forms of Skelid: Tablet Oral
Chemical IUPAC Name: [(4-chlorophenyl)sulfanyl-phosphonomethyl]phosphonic acid
Chemical Formula: C7H9ClO6P2S
Tiludronate on Wikipedia: https://en.wikipedia.org/wiki/Tiludronate
Organisms Affected: Humans and other mammals
