U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C7H9ClO6P2S
Molecular Weight 318.608
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TILUDRONIC ACID

SMILES

OP(O)(=O)C(SC1=CC=C(Cl)C=C1)P(O)(O)=O

InChI

InChIKey=DKJJVAGXPKPDRL-UHFFFAOYSA-N
InChI=1S/C7H9ClO6P2S/c8-5-1-3-6(4-2-5)17-7(15(9,10)11)16(12,13)14/h1-4,7H,(H2,9,10,11)(H2,12,13,14)

HIDE SMILES / InChI

Molecular Formula C7H9ClO6P2S
Molecular Weight 318.608
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Tiludronic acid is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates. 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. Tiludronic acid is marketed under the tradename Skelid. In vitro studies indicate that tiludronate disodium 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. Tiludronate disodium appears to inhibit osteoclasts through 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. SKELID is indicated for treatment of Paget's disease of bone (osteitis deformans).

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SKELID

Cmax

ValueDoseCo-administeredAnalytePopulation
1.1 mg/L
200 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens
2.3 mg/L
400 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens
4.7 mg/L
600 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens
7.8 mg/L
800 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
10.3 mg × h/L
200 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens
25 mg × h/L
400 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens
46.8 mg × h/L
600 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens
80 mg × h/L
800 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
78 h
400 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens
65.7 h
600 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens
72 h
800 mg 1 times / day multiple, oral
TILUDRONIC ACID plasma
Homo sapiens

Doses

AEs

PubMed

Sample Use Guides

In Vivo Use Guide
A single 400-mg daily oral dose of SKELID (Tiludronic acid), taken with 6 to 8 ounces of plain water only, should be administered for a period of 3 months. Beverages other than plain water (including mineral water), food (see below), and some medications. Patients should not lie down for at least 30 minutes after taking this medication. SKELID should not be taken within 2 hours of food.
Route of Administration: Oral
In Vitro Use Guide
The ability of tiludronate to inhibit proton transport was 5-fold higher in kidney-derived chicken vesicles (IC50 = 1.1 mM) and 10,000-fold higher in vesicles derived from chicken osteoclasts (IC50 = 466 nM). Tiludronate also potently inhibited proton transport in yeast microsomal preparations (IC50 = 3.5 uM) and inhibited the activity of purified yeast V-ATPase.
Substance Class Chemical
Record UNII
6PNS59HP4Y
Record Status Validated (UNII)
Record Version