Clodronate Disodium

Names

[ Name ]:
Clodronate Disodium

[Synonym ]:
Clastoban
Clodronic acid disodium salt
Cl2MDP Clodronate disodium Clodronic acid disodium salt DMDP
Bonefos
UNII-Y05R4GCQ1H
(Dichloromethylene)diphosphonic acid,disodium salt
Phosphonic acid, (dichloromethylene)bis-, sodium salt (1:2)
EINECS 245-078-9
MFCD01632786
Clasteon
Lytos
Ossiten
Sodium clodronate
disodium,[dichloro-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate
Loron
Disodium Clodronate
Mebonat
Clodronate Disodium
Clodronic Acid, Disodium Salt, Hydrate
disodium (dichloromethanediyl)bis[hydrogen (phosphonate)]
Disodium (dichloromethylene)bis[hydrogen (phosphonate)]
Ostac
Dichloromethylenediphosphonic acid disodium salt

Biological Activity

[Description]:

Clodronic acid (Clodronate) disodium salt, a first-generation bisphosphonate, is orally active osteoclastic bone resorption inhibitor. Clodronic acid disodium salt can be used in high bone turnover states, Paget’s disease and osteolytic bone metastases[1][2][3].

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

[In Vitro]

Clodronic acid (Clodronate) disodium salt induces rapid apoptosis in osteoclasts by preventing translocation of ADP into mitochondria after being internalised via resorption. Consequently, ATP production is inhibited, leading to induction of apoptosis by means of release of cytochrome C into the cytoplasm[2].

[In Vivo]

Clodronic acid (Clodronate) disodium salt (6.25-25 mg/kg; p.o.; daily for 28 days) slightly decreases the hindpaw swelling at doses of 12.5 and 25 mg/kg[3]. Animal Model: Male Lewis rats, aged 7 weeks[3] Dosage: 6.25, 12.5, and 25 mg/kg Administration: P.o.; daily for 28 days Result: Hindpaw swelling was significantly smaller than in adjuvant-arthritis (AA)-control at 25 mg/kg on days 21 and 28 (87 and 88% of AA-control, respectively) and at 12.5 mg/kg on day 28.

[References]

[1]. Mönkkönen J, et al. Clodronate (dichloromethylene bisphosphonate) inhibits LPS-stimulated IL-6 and TNF production by RAW 264 cells. Life Sci. 1994;54(14):PL229‐PL234.

[2]. Tanakol R, et al. Clodronic acid in the treatment of postmenopausal osteoporosis. Clin Drug Investig. 2007;27(6):419‐433.

[3]. Itoh F, et al. Effects of clodronate and alendronate on local and systemic changes in bone metabolism in rats with adjuvant arthritis. Inflammation. 2004;28(1):15‐21.

Chemical & Physical Properties

[ Density]:
2.306g/cm3

[ Boiling Point ]:
474.7ºC at 760mmHg

[ Melting Point ]:
>330ºC

[ Molecular Formula ]:
CH₂Cl₂Na₂O₆P₂

[ Molecular Weight ]:
288.856

[ Flash Point ]:
240.9ºC

[ Exact Mass ]:
287.849915

[ PSA ]:
140.34000

[ LogP ]:
1.30710

[ Vapour Pressure ]:
2.55E-10mmHg at 25°C

[ Storage condition ]:
-20°C Freezer

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: SZ7640700

CHEMICAL NAME :: Phosphonic acid, (dichloromethylene)bis-, disodium salt

CAS REGISTRY NUMBER :: 22560-50-5

LAST UPDATED :: 199512

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C-H2-Cl2-O6-P2.2Na

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3600 mg/kg/15D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - proteinuria Kidney, Ureter, Bladder - hematuria Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :: TOPADD Toxicologic Pathology. (c/o Dr. F.A. de la Iglesia, Warner-Lambert Co., Pharmaceutical Research Div., POB 1047, Ann Arbor, MI 48106) V.6(3/4)- 1978- Volume(issue)/page/year: 17,27,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1200 mg/kg/3D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - hematuria Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :: TOPADD Toxicologic Pathology. (c/o Dr. F.A. de la Iglesia, Warner-Lambert Co., Pharmaceutical Research Div., POB 1047, Ann Arbor, MI 48106) V.6(3/4)- 1978- Volume(issue)/page/year: 17,27,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - pig

DOSE/DURATION :: 182 gm/kg/26W-I

TOXIC EFFECTS :: Musculoskeletal - changes in teeth and supporting structures Musculoskeletal - other changes Related to Chronic Data - death

REFERENCE :: APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 59,129,1986

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
SZ7640700

[ HS Code ]:
2931900090

Customs

[ HS Code ]: 2931900090

[ Summary ]:
2931900090. other organo-inorganic compounds. VAT:17.0%. Tax rebate rate:13.0%. Supervision conditions:AB(certificate of inspection for goods inward,certificate of inspection for goods outward). MFN tariff:6.5%. General tariff:30.0%

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