Tiludronic acid (INN; also known as tiludronate) is a bisphosphonate used for treatment of Paget's disease of bone (osteitis deformans) in human being 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.
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 than nitrogenous bisphosphonates.
Tiludronate has been used primarily for the treatment of diseases in horses that are associated with inappropriate osteolysis, such as navicular disease[4] and osteoarthritis. It has specifically been shown to improve lameness in horses with osteoarthritis of the distal hock joints (bone spavin)[5] and vertebral column.[6]
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.[7] 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.[8] 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.[9] 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.[10]
Signs of colic, which is usually self-limiting, occurs in 30-45% of horses.
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 (2008). "A review of the Efficacy of Tiludronate in the Horse". Journal or Equine Veterinary Science. 28 (4): 209–214. doi:10.1016/j.jevs.2008.02.007.
^Rogers MJ, Crockett JC, Coxon FP, Mönkkönen J (July 2011). "Biochemical and molecular mechanisms of action of bisphosphonates". Bone. 49 (1): 34–41. doi:10.1016/j.bone.2010.11.008. PMID 21111853.
^Tripathi KD (2013-09-30). Essentials of medical pharmacology (Seventh ed.). New Delhi. ISBN9789350259375. OCLC 868299888.{{cite book}}: CS1 maint: location missing publisher (link)
^Denoix JM, Thibaud D, Riccio B (June 2003). "Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double-blind placebo-controlled clinical trial". Equine Veterinary Journal. 35 (4): 407–13. doi:10.2746/042516403776014226. PMID 12880010.
^Gough MR, Thibaud D, Smith RK (July 2010). "Tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial". Equine Veterinary Journal. 42 (5): 381–7. doi:10.1111/j.2042-3306.2010.00120.x. PMID 20636772.
^Coudry V, Thibaud D, Riccio B, Audigié F, Didierlaurent D, Denoix JM (March 2007). "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. 68 (3): 329–37. doi:10.2460/ajvr.68.3.329. PMID 17331024.
^Delguste C, Amory H, Guyonnet J, Thibaud D, Garnero P, Detilleux J, et al. (April 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 (2): 108–16. doi:10.1111/j.1365-2885.2007.00936.x. PMID 18307502.
^Allen KA, Johns S, Hyman SS, Sislak MD, Davis S, Amory J (December 2010). "How to Diagnose and Treat Back Pain in the Horse" (PDF). AAEP Proceedings. 56: 384–388.
^Duesterdieck-Zellmer KF, Driscoll N, Ott JF (October 2012). "Concentration-dependent effects of tiludronate on equine articular cartilage explants incubated with and without interleukin-1β". American Journal of Veterinary Research. 73 (10): 1530–9. doi:10.2460/ajvr.73.10.1530. PMID 23013178.
^U.S. Food and Drug Administration. "FDA Provides Equine Veterinarians with Important Information about TILDREN and OSPHOS for Navicular Syndrome in Horses". Retrieved 3 January 2015.
External links
Prescribing information for Skelid
RxList page
tildren.com
August 22, 2023
tiludronic, acid, also, known, tiludronate, bisphosphonate, used, treatment, paget, disease, bone, osteitis, deformans, human, being, medicine, tradename, skelid, veterinary, medicine, tiludronic, acid, used, treat, navicular, disease, bone, spavin, horses, tr. Tiludronic acid INN also known as tiludronate is a bisphosphonate used for treatment of Paget s disease of bone osteitis deformans in human being 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 Tiludronic acidClinical dataTrade namesSkelidAHFS Drugs comInternational Drug NamesATC codeM05BA05 WHO Legal statusLegal statusCA onlyIdentifiersIUPAC name 4 Chlorophenyl thio methylene bis phosphonic acid CAS Number89987 06 4 YPubChem CID60937IUPHAR BPS7604DrugBankDB01133 NChemSpider54905 NUNII6PNS59HP4YKEGGD08599 NChEMBLChEMBL1350 NCompTox Dashboard EPA DTXSID10237966ECHA InfoCard100 121 105Chemical and physical dataFormulaC 7H 9Cl O 6P 2SMolar mass318 60 g mol 13D model JSmol Interactive imageSMILES c1cc ccc1SC P O O O P O O O ClInChI 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 NKey DKJJVAGXPKPDRL UHFFFAOYSA N N N Y what is this verify 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 linksMechanism of action EditTiludronate 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 than nitrogenous bisphosphonates Relative potency 3 Bisphosphonate Relative potencyEtidronate 1Tiludronate 10Pamidronate 100Aledronate 100 500Ibandronate 500 1000Risedronate 1000Zoledronate 5000Use in equine medicine EditTiludronate has been used primarily for the treatment of diseases in horses that are associated with inappropriate osteolysis such as navicular disease 4 and osteoarthritis It has specifically been shown to improve lameness in horses with osteoarthritis of the distal hock joints bone spavin 5 and vertebral column 6 Method of administration Edit 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 7 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 8 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 9 Further studies are needed to evaluate the safety of Tildren administration via RLP Adverse reactions and contraindications Edit Tildren has been shown to have several adverse effects 10 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 Edit Kamm L McIlwraith W Kawcak C 2008 A review of the Efficacy of Tiludronate in the Horse Journal or Equine Veterinary Science 28 4 209 214 doi 10 1016 j jevs 2008 02 007 Rogers MJ Crockett JC Coxon FP Monkkonen J July 2011 Biochemical and molecular mechanisms of action of bisphosphonates Bone 49 1 34 41 doi 10 1016 j bone 2010 11 008 PMID 21111853 Tripathi KD 2013 09 30 Essentials of medical pharmacology Seventh ed New Delhi ISBN 9789350259375 OCLC 868299888 a href Template Cite book html title Template Cite book cite book a CS1 maint location missing publisher link Denoix JM Thibaud D Riccio B June 2003 Tiludronate as a new therapeutic agent in the treatment of navicular disease a double blind placebo controlled clinical trial Equine Veterinary Journal 35 4 407 13 doi 10 2746 042516403776014226 PMID 12880010 Gough MR Thibaud D Smith RK July 2010 Tiludronate infusion in the treatment of bone spavin a double blind placebo controlled trial Equine Veterinary Journal 42 5 381 7 doi 10 1111 j 2042 3306 2010 00120 x PMID 20636772 Coudry V Thibaud D Riccio B Audigie F Didierlaurent D Denoix JM March 2007 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 68 3 329 37 doi 10 2460 ajvr 68 3 329 PMID 17331024 Delguste C Amory H Guyonnet J Thibaud D Garnero P Detilleux J et al April 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 2 108 16 doi 10 1111 j 1365 2885 2007 00936 x PMID 18307502 Allen KA Johns S Hyman SS Sislak MD Davis S Amory J December 2010 How to Diagnose and Treat Back Pain in the Horse PDF AAEP Proceedings 56 384 388 Duesterdieck Zellmer KF Driscoll N Ott JF October 2012 Concentration dependent effects of tiludronate on equine articular cartilage explants incubated with and without interleukin 1b American Journal of Veterinary Research 73 10 1530 9 doi 10 2460 ajvr 73 10 1530 PMID 23013178 U S Food and Drug Administration FDA Provides Equine Veterinarians with Important Information about TILDREN and OSPHOS for Navicular Syndrome in Horses Retrieved 3 January 2015 External links EditPrescribing information for Skelid RxList page tildren com Retrieved from https en wikipedia org w index php title Tiludronic acid amp oldid 1171452781, wikipedia, wiki, book, books, library,
