化合物信息

Drug Groups

approved

Description

Tiludronate is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates.

Indication

For treatment of Paget's disease of bone (osteitis deformans).

Pharmacology

Tiludronate is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and clodronate. Tiludronate 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.

Toxicity

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.

Affected Organisms

Biotransformation

In vitro, tiludronic acid is not metabolized in human liver microsomes and hepatocytes. There is no evidence that tiludronate is metabolized in humans.

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.

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.

Protein Binding

Approximately 90% bound to human serum protein (mainly albumin) at plasma concentrations between 1 and 10 mg/L.

Elimination

The principal route of elimination of tiludronic acid is in the urine.

Clearance

* renal cl=10 mL/min [IV administration of 20-mg dose]

References

External Links