Clodronate

Các tên gọi khác (13 ) :

(Dichloro-phosphono-methyl)-phosphonic acid
(Dichloromethylene)bisphosphonic acid
(Dichloromethylene)diphosphonic acid
Acide Clodronique
Acido Clodronico
Acidum Clodronicum
Clodronate
Clodronsaeure
Clodronsäure
Dichloromethanediphosphonic acid
Dichloromethylene-1,1-bisphosphonic acid
Dichloromethylene-1,1-diphosphonic acid
Dichloromethylidene diphosphonate

bone density conservation agents, antihypocalcemic agents, bisphosphonates

Thuốc Gốc

Small Molecule

CAS: 10596-23-3

ATC: M05BA02

CTHH: CH₄Cl₂O₆P₂

PTK: 244.892

A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. [PubChem]

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

CH₄Cl₂O₆P₂

Phân tử khối

244.892

Monoisotopic mass

243.886016298

InChI

InChI=1S/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9)

InChI Key

InChIKey=ACSIXWWBWUQEHA-UHFFFAOYSA-N

IUPAC Name

[dichloro(phosphono)methyl]phosphonic acid

Traditional IUPAC Name

dichloro(phosphono)methylphosphonic acid

SMILES

OP(O)(=O)C(Cl)(Cl)P(O)(O)=O

Độ tan chảy

250 °C

Độ hòa tan

395 mg/L

logP

-2.4

logS

-1.5

pKa (strongest acidic)

0.62

PSA

115.06 Å²

Refractivity

38.21 m³·mol^-1

Polarizability

15.3 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

-2

Number of Rings

Bioavailability

Rule of Five

true

Dược Lực Học : Clodronate is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and tiludronate. Clodronate affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the clodronate 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. Clodronate has been shown to prevent or delay skeletal-related events and decrease bone pain as well as normalize calcium levels in the presence of hypercalcemia.

Cơ Chế Tác Dụng : A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. [PubChem] The bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. The exact mechanism of action of clodronate is not known, however it is known that it does not inhibit protein isoprenylation but can be metabolized intracellularly to a β-γ-methylene (AppCp-type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Inhibition of the ADP/ATP translocase by the metabolite AppCCl2p is a likely route by which clodronate causes osteoclast apoptosis and inhibits bone resorption. Recently, the slime mold Dictyostelium discoideum was shown to take up bisphosphonates by pinocytosis. In these cells, clodronate, but not other pharmacologically active bisphosphonates, was incorporated into adenine nucleotides, which could potentially explain why this bisphosphonate sometimes seems to act differently than the other bisphosphonates. Clodronate, like all biphosphonates, also binds protein-tyrosine-phosphatase.

Dược Động Học :

▧ Absorption :
After oral administration, absorption is estimated at 1–3% of the ingested dose because of the low uptake from the gastrointestinal tract.
▧ Protein binding :
2%-36%
▧ Metabolism :
Clodronate is not metabolized in humans.
▧ Half Life :
Approximately 13 hours.

Độc Tính : Decreases in serum calcium following substantial overdosage may be expected in some patients. Signs and symptoms of hypocalcemia also may occur in some of these patients.

Chỉ Định : For the management of hypercalcemia of malignancy and as an adjunct in the management of osteolysis resulting from bone metastases of malignant tumors.

Tương Tác Thuốc :

Aluminium Formation of non-absorbable complexes
Calcium Formation of non-absorbable complexes
Calcium Acetate Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives such as clodronate. Avoid administration of oral calcium supplements within 2 hours before or after tiludronate/clodronate/etidronate.
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.
Dihydroxyaluminium Formation of non-absorbable complexes
Estramustine Clodronate may increase the levels of estramustine.
Iron Formation of non-absorbable complexes
Iron Dextran Formation of non-absorbable complexes
Magnesium Formation of non-absorbable complexes
Magnesium oxide Formation of non-absorbable complexes
Sucralfate Formation of non-absorbable complexes

Liều Lượng & Cách Dùng : Capsule - Oral - 400 mg
Solution - Intravenous - 30 mg/ml
Solution - Intravenous - 60 mg/ml

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Clasteon 400 mg Capsule

Giá bán buôn : USD >1.36

Đơn vị tính : capsule
Biệt dược thương mại : Bonefos 400 mg Capsule

Giá bán buôn : USD >2.04

Đơn vị tính : capsule
Biệt dược thương mại : Bonefos 60 mg/ml

Giá bán buôn : USD >13.69

Đơn vị tính : ml

Nhà Sản Xuất

Công ty : Bayer

Sản phẩm biệt dược : Bonefos
Công ty : Sepracor

Sản phẩm biệt dược : Clasteon
Công ty : Boehringer Ingelheim

Sản phẩm biệt dược : Lodronat
Công ty : Roche

Sản phẩm biệt dược : Loron
Công ty : Roche

Sản phẩm biệt dược : Lytos
Công ty : Roche

Sản phẩm biệt dược : Ostac
Công ty : Sindan

Sản phẩm biệt dược : Sindronat

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00720

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=25419

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508646

ChemSpider

http://www.chemspider.com/Chemical-Structure.23731.html

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50216172

PharmGKB

http://www.pharmgkb.org/drug/PA10239

Wikipedia

http://en.wikipedia.org/wiki/Clodronate

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