Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/06/12 00:22:11」(JST)
[Wiki en表示]
Tiludronic acid
|
| Clinical data |
| Trade names |
Skelid |
| AHFS/Drugs.com |
International Drug Names |
| ATC code |
|
| Identifiers |
IUPAC name
- {[(4-Chlorophenyl)thio]methylene}bis(phosphonic acid)
|
| CAS Number |
|
| PubChem CID |
|
| IUPHAR/BPS |
|
| DrugBank |
|
| ChemSpider |
|
| UNII |
|
| KEGG |
|
| ChEMBL |
|
| ECHA InfoCard |
100.121.105 |
| Chemical and physical data |
| Formula |
C7H9ClO6P2S |
| Molar mass |
318.609 g/mol |
| 3D model (Jmol) |
|
SMILES
-
c1cc(ccc1SC(P(=O)(O)O)P(=O)(O)O)Cl
|
InChI
-
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) N
-
Key:DKJJVAGXPKPDRL-UHFFFAOYSA-N N
|
| NY (what is this?) (verify) |
Tiludronic acid (INN; also known as tiludronate) is a bisphosphonate used for treatment of Paget's disease of bone (osteitis deformans) in human medicine. It has the tradename Skelid. In veterinary medicine, tiludronic acid is used to treat navicular disease and bone spavin in horses. Its tradenames are Tildren and Equidronate. It is approved for treatment of navicular disease and distal tarsal osteoarthritis in Europe,[1] and was approved for treatment of navicular disease in the United States in 2014.
Contents
- 1 Mechanism of action
- 2 Use in equine medicine
- 2.1 Method of administration
- 2.2 Adverse reactions and contraindications
- 3 References
- 4 External links
Mechanism of action
Tiludronate is a non-nitrogenous bisphosphonate that inhibits osteoclasts, the primary cell responsible for the breakdown of bone required for bone remodeling. Non-nitrogenous bisphosphonates are metabolized by osteoclasts to compounds that then replace a portion of the adenosine triphosphate (ATP) molecule, making it non-functional. These non-functional molecules then competitively inhibit ATP in the cell, reducing cell energy and leading to apoptosis.[2] Decreased levels of osteoclasts subsequently reduce the degree of breakdown of bone and bone turnover. Non-nitrogenous bisphosphonates are less potent relative to nitrogenous bisphosphonates.
Use in equine medicine
Tiludronate has been used primarily for the treatment of diseases in horses that are associated with inappropriate osteolysis, such as navicular disease[3] and osteoarthritis. It has specifically been shown to improve lameness in horses with osteoarthritis of the distal hock joints (bone spavin)[4] and vertebral column.[5]
Method of administration
Tildren is administered intravenously. It is labeled for 0.1 mg/kg dosing, once daily for 10 days by slow intravenous injection, which for a 500 kg horse works out to be 1 vial per day. However, one study giving all 10 doses at once (1 mg/kg IV as a single CRI) was found to have the same pharmacological effects, and is used clinically.[6] It may be given systemically or locally, by regional limb perfusion. Although RLP is thought to have certain benefits, including decreased cost and reduced risk of adverse effects, some diseases must be treated systemically, such as osteoarthritis of the vertebral column. Systemic administration is often given by adding a 1 mg/kg dose into a 1 liter fluid bag, which is slowly given over 60–90 minutes. Its effects are reported to last 4 months or longer, with a peak effect 6–8 weeks post treatment.[7] The effects of regional limb perfusion has come into question due to in vitro studies showing that high doses given by RLP or intraarticular injection may damage articular cartilage by chondrocyte apoptosis.[8] Further studies are needed to evaluate the safety of Tildren administration via RLP.
Adverse reactions and contraindications
Tildren has been shown to have several adverse effects.[9]
- Signs of colic, which is usually self-limiting, occurs in 30-45% of horses.
- Tachycardia
- Electrolyte disturbances: primarily calcium, magnesium, and potassium, which can last for several hours. Caution should be used in horses with disease processes that could be affected by electrolyte disturbances, such as hyperkalemic periodic paralysis or cardiac disease.
- Kidney damage: it is eliminated by the kidney and is not recommended for use in animals with impaired renal function.
- Less serious reactions include stiffness of the neck, decreased appetite, fever, and increased urination.
It is not recommended for animals under four years of age, due to lack of studies evaluating its safety in growing animals, nor for pregnant or lactating animals, since its effect on the fetus has not been studied.
References
- ^ Kamm L, McIlwraith W, Kawcak C. A review of the Efficacy of Tiludronate in the Horse. Journal or Equine Veterinary Science. Vol 28(4): 209-214.
- ^ Rogers MJ, Crockett JC, Coxon FP, Monkkonen J. 2011. Biochemical and molecular mechanisms of action of bisphosphonates. Bone 49:34-41
- ^ DENOIX, J.M., THIBAUD, D. and RICCIO, B. (2003), Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double-blind placebo-controlled clinical trial. Equine Veterinary Journal, 35: 407–413. doi: 10.2746/042516403776014226
- ^ GOUGH, M. R., THIBAUD, D. and SMITH, R. K. W. (2010), Tiludronate infusion in the treatment of bone spavin: A double blind placebo-controlled trial. Equine Veterinary Journal, 42: 381–387. doi: 10.1111/j.2042-3306.2010.00120
- ^ V. Coudry, D. Thibaud; B. Riccio; F. Audigié; D. Didierlaurent; M Denoix. Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column. American Journal of Veterinary Research. Vol. 68, No. 3, Pages 329-337 March 2007
- ^ DELGUSTE, C., AMORY, H., GUYONNET, J., THIBAUD, D., GARNERO, P., DETILLEUX, J., LEPAGE, O. M. and DOUCET, M. (2008), Comparative pharmacokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX-1. Journal of Veterinary Pharmacology and Therapeutics, 31: 108–116. doi: 10.1111/j.1365-2885.2007.00936
- ^ Allen KA, Johns S, Hyman SS, Sislak MD, Davis S, Amory J. How to Diagnose and Treat Back Pain in the Horse. Proc. AAEP. Vol 56: 384-388
- ^ Duesterdieck-Zellmer KF, Driscoll N, Ott JF. Concentration-dependent effects of tiludronate on equine articular cartilage explants incubated with and without interleukin-1β. American Journal of Veterinary Research. Oct 2012, Vol. 73, No. 10, Pages 1530-1539. doi: 10.2460/ajvr.73.10.1530
- ^ U.S. Food and Drug Administration. "FDA Provides Equine Veterinarians with Important Information about TILDREN and OSPHOS for Navicular Syndrome in Horses". http://www.fda.gov/AnimalVeterinary/ResourcesforYou/ucm406581.htm.
External links
- Prescribing information for Skelid
- RxList page
- tildren.com
|
Drugs for treatment of bone diseases (M05)
|
| Bisphosphonates |
- Nitrogenous (Alendronic acid
- ibandronic acid
- incadronic acid
- pamidronic acid
- risedronic acid
- zoledronic acid)
Non-nitrogenous (Etidronic acid
- clodronic acid
- tiludronic acid)
|
| Bone morphogenetic proteins |
- Dibotermin alfa
- Eptotermin alfa
|
| Other |
- Resorption inhibitor (Ipriflavone)
- Aluminium chlorohydrate
- Dual action bone agent (Strontium ranelate)
RANKL inhibitor (Denosumab)- Cathepsin K inhibitor (Odanacatib)
- Calcium
- Vitamin D
|
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Interaction between a bisphosphonate, tiludronate, and biomimetic nanocrystalline apatites.
- Pascaud P, Gras P, Coppel Y, Rey C, Sarda S.SourceCIRIMAT, INPT-CNRS-UPS, Université de Toulouse, Université Paul Sabatier, Toulouse, France.
- Langmuir : the ACS journal of surfaces and colloids.Langmuir.2013 Feb 19;29(7):2224-32. doi: 10.1021/la3046548. Epub 2013 Feb 4.
- Bisphosphonates (BPs) are well established as successful antiresorptive agents for the prevention and treatment of bone diseases such as osteoporosis and Paget's disease. The aim of this work was to clarify the reaction mechanisms between a BP molecule, tiludronate, and the nanocrystalline apatite s
- PMID 23317459
- Concentration-dependent effects of tiludronate on equine articular cartilage explants incubated with and without interleukin-1β.
- Duesterdieck-Zellmer KF, Driscoll N, Ott JF.SourceDepartment of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA. katja.zellmer@oregonstate.edu
- American journal of veterinary research.Am J Vet Res.2012 Oct;73(10):1530-9.
- OBJECTIVE: To determine concentration-dependent effects of tiludronate on cartilage explants incubated with or without recombinant equine interleukin-1β (rEq IL-1).SAMPLE: Articular cartilage explants from the femorotibial joints of 3 young adult horses.PROCEDURES: Cartilage explants were incubated
- PMID 23013178
- Interaction between a bisphosphonate, tiludronate and nanocrystalline apatite: in vitro viability and proliferation of HOP and HBMSC cells.
- Pascaud P, Bareille R, Bourget C, Amédée J, Rey C, Sarda S.SourceCIRIMAT Carnot Institute, Université de Toulouse,CNRS/INPT/UPS, ENSIACET, 4 Allée Emile Monso, BP 44362, 31030 Toulouse Cedex 04, France.
- Biomedical materials (Bristol, England).Biomed Mater.2012 Oct;7(5):054108. doi: 10.1088/1748-6041/7/5/054108. Epub 2012 Sep 12.
- Nanocrystalline apatites (NCA) are the inorganic components of mineralized tissues and they have been recently proposed as biomaterials for drug delivery systems. Bisphosphonates (BPs) are currently the reference drugs used to treat diseases involving bone disorders such as osteoporosis. Nevertheles
- PMID 22972389
Japanese Journal
- ビスフォスフォネートの好中球由来マトリックスメタロプロテアーゼ活性に与える影響
- Identification of adenine nucleotide-containing metabolites of bisphosphonate drugs using ion-pair liquid chromatography-electrospray mass spectrometry
- Journal of chromatography. B, Biomedical sciences and applications 704(1), 187-195, 1997-12-19
- NAID 10024524710
- Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts
Related Links
- You should eat and drink plenty of foods and drinks that are rich in calcium and vitamin D while you are taking tiludronate Your doctor will tell you which foods and drinks are good sources of these nutrients and how many ...
- Tiludronate is in the group of medicines called bisphosphonates (bis FOS fo nayts). It alters the cycle of bone formation and breakdown in the body. Tiludronate is used to treat Paget's disease of bone. Tiludronate may also be used ...
Related Pictures
★リンクテーブル★
[★]
- 英
- tiludronate、tiludronic acid、tiludronate disodium
- 関
- チルドロネート、チルドロン酸二ナトリウム
[★]
- 関
- tiludronate、tiludronate disodium
[★]
- 英
- tiludronate
- 関
- チルドロン酸
[★]
- 関
- tiludronate、tiludronic acid