Tìm theo
Tiludronate
Các tên gọi khác (5 ) :
  • Acide tiludronique
  • Acido tiludronico
  • Acidum tiludronicum
  • Tiludronate
  • Tiludronic acid
bone density conservation agents, antihypocalcemic agents
Thuốc Gốc
Small Molecule
CAS: 89987-06-4
ATC: M05BA05
ĐG : Sanofi-Aventis Inc. , http://www.sanofi-aventis.com
CTHH: C7H9ClO6P2S
PTK: 318.608
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C7H9ClO6P2S
Phân tử khối
318.608
Monoisotopic mass
317.928359441
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)
InChI Key
InChIKey=DKJJVAGXPKPDRL-UHFFFAOYSA-N
IUPAC Name
{[(4-chlorophenyl)sulfanyl](phosphono)methyl}phosphonic acid
Traditional IUPAC Name
[(4-chlorophenyl)sulfanyl](phosphono)methylphosphonic acid
SMILES
OP(O)(=O)C(SC1=CC=C(Cl)C=C1)P(O)(O)=O
Độ hòa tan
6.97e+00 g/l
logP
-0.6
logS
-1.7
pKa (strongest acidic)
1.03
PSA
115.06 Å2
Refractivity
65.11 m3·mol-1
Polarizability
25.37 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
6
H Bond Donor Count
4
Physiological Charge
-2
Number of Rings
1
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. The bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. In vitro studies indicate that tiludronate 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 appears to inhibit osteoclasts by 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.
Dược Động Học :
▧ 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.
▧ Protein binding :
Approximately 90% bound to human serum protein (mainly albumin) at plasma concentrations between 1 and 10 mg/L.
▧ Metabolism :
In vitro, tiludronic acid is not metabolized in human liver microsomes and hepatocytes. There is no evidence that tiludronate is metabolized in humans.
▧ Route of Elimination :
The principal route of elimination of tiludronic acid is in the urine.
▧ 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.
▧ Clearance :
* renal cl=10 mL/min [IV administration of 20-mg dose]
Độc Tính : 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.
Chỉ Định : For treatment of Paget's disease of bone (osteitis deformans).
Tương Tác Thuốc :
  • Calcium Acetate The divalent cation of oral Calcium Acetate may significantly decrease the absorption of Tiludronate by forming a nonabsorbable chelate. Oral dosing should be separated by at least 2 hours.
  • Calcium Chloride Calcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 2 hours before or after tiludronate/clodronate/etidronate.
  • Magnesium oxide The divalent cation of oral Magnesium oxide may significantly decrease the absorption of Tiludronate by forming a nonabsorbable chelate. Oral dosing should be separated by at least 2 hours.
  • Magnesium Sulfate The divalent cation of oral Magnesium sulfate may significantly decrease the absorption of Tiludronate by forming a nonabsorbable chelate. Oral dosing should be separated by at least 2 hours.
Liều Lượng & Cách Dùng : Tablet - Oral - 200 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Skelid 200 mg tablet
    Giá bán buôn : USD >11.47
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Skelid
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01133
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=60937
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505302
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C08141
ChemSpider
http://www.chemspider.com/Chemical-Structure.54905.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0024-1800-16
PharmGKB
http://www.pharmgkb.org/drug/PA451688
Wikipedia
http://en.wikipedia.org/wiki/Tiludronate
RxList
http://www.rxlist.com/cgi/generic2/tiludronate.htm
Drugs.com
http://www.drugs.com/cdi/tiludronate.html
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