Tiludronic acid

Absorption

A single 400mg dose of tiludronic acid reaches a Cmax of 3.35±1.07mg/L, with a Tmax of 1.7—0.9h, and and AUC of 27.2±9.0mg*h/L. Tiludronic acid has an oral bioavailability of 2-11% with an average of 6%.

Toxicity

Patients experiencing an overdose may present with hypocalcemia. Patients given doses of 6mg/kg/day for 2 days have experienced acute renal failure and death. Treat overdose with symptomatic and supportive care. Dialysis will not be useful for removal of the drug from serum.

Background

Tiludronate, or (4-chlorophenyl)thio-methylene-1,1-bisphosphonate, is a first generation bisphosphonate similar to etidronic acid and clodronic acid. These drugs were developed to mimic the action of pyrophosphate, a regulator of calcification and decalcification. Tiludronic acid was first described in the literature in 1988 as a potential treatment for Paget's disease of bone.
Tiludronic acid was granted FDA approval on 7 March 1997.

Indications

Tiludronic acid is indicated to treat Paget's disease of bone in patients with serum alkaline phosphatase levels ≥2 times the upper limit of normal, with symptoms, or with risk of future complications.

Definition

ChEBI: Tiludronic acid is an organochlorine compound.

Pharmacokinetics

Tiludronic acid is a bisphosphonate that prevents osteoclasts from resorbing bone. The duration of action is quite long due to the slow clearance from the bone, and the therapeutic window is wide. Patients should be counselled regarding the risk of upper GI mucosal irritation as well as gastric and duodenal ulcers.

Veterinary Drugs and Treatments

Tiludronate disodium (tiludronic acid) is a bisphosphonate bone resorption inhibitor that is available in some countries for the intravenous treatment of navicular disease in horses. Treatment earlier in the course of the disease apparently results in greater efficacy.
For humans, there is an orally administered FDA-approved product for treating Paget’s disease (osteitis deformans).

Metabolism

Tiludronic acid is not metabolized in vitro in human liver microsomes.