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药品详细

Alendronate(阿仑膦酸钠)

化学结构式图
中文名
阿仑膦酸钠
英文名
Alendronate
分子式
C4H13NO7P2
化学名
(4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid
分子量
Average: 249.096
Monoisotopic: 249.016724799
CAS号
66376-36-1
ATC分类
M05B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Alendronate is a nitrogen-containing, second generation bisphosphonate. Bisphosphonates were first used to treat Paget’s disease in 1971. This class of medications is comprised of inorganic pyrophosphate analogues that contain non-hydrolyzable P-C-P bonds. Similar to other bisphosphonates, alendronate has a high affinity for bone mineral and is taken up during osteoclast resorption. Alendronate inhibits farnesyl pyrophosphate synthetase, one of the enzymes in the mevalonic acid pathway involved in producing isoprenoid compounds that are essential for post-translational modification of small guanosine triphosphate (GTP)-binding proteins, such as Rho, Ras and Rab. Inhibition of this process interferes with osteoclast function and survival. Alendronate is used for the treatment of osteoporosis and Paget’s disease.

生产厂家
  • Apotex inc
  • Aurobindo pharma ltd
  • Austarpharma llc
  • Barr laboratories inc
  • Cadista pharmaceuticals inc
  • Dr reddys laboratories ltd
  • Genpharm ulc
  • Merck and co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Sun pharma global inc
  • Teva pharmaceuticals usa
  • Watson laboratories
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Russell RG, Watts NB, Ebetino FH, Rogers MJ: Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008 Jun;19(6):733-59. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Bisphosphonates
Substructures
  • Hydroxy Compounds
  • Carboxylic Acids and Derivatives
  • Phosphonic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Phosphinic Acids and Derivatives
  • Bisphosphonates
适应症
药理
Indication For the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women.
Pharmacodynamics Alendronate, a second-generation bisphosphonate is the first member of a group of drugs which strengthens bone. Alendronate is used to reduce hypercalcemia in tumor-induced bone disease, to treat corticosteroid-induced osteoporosis and Paget's disease, and to prevent osteoporosis in postmenopausal women.
Mechanism of action The action of Alendronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.
Absorption Relative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women (0.78%) when administered after an overnight fast and 2 hours before breakfast.
Volume of distribution
  • 28 L
Protein binding 78%
Metabolism
There is no evidence that alendronate is metabolized in humans or animals.
Route of elimination Following a single IV dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces.
Half life >10 years
Clearance
  • <200 mL/min [A single 10 mg IV dose]
Toxicity Alendronate can damage the esophagus both by toxicity from the medication itself and by nonspecific irritation secondary to contact between the pill and the esophageal mucosa, similar to other cases of "pill esophagitis."
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00095 Alendronate pathway SMP00095
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 234 dec °C PhysProp
water solubility 1mg/L Not Available
logP -4.3 Not Available
pKa 2.72 (at 25 °C) MERCK INDEX (1996)
Predicted Properties
Property Value Source
water solubility 1.69e+01 g/l ALOGPS
logP -1.3 ALOGPS
logP -4.2 ChemAxon
logS -1.2 ALOGPS
pKa (strongest acidic) 0.69 ChemAxon
pKa (strongest basic) 9.91 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 8 ChemAxon
hydrogen donor count 6 ChemAxon
polar surface area 161.31 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 47.37 ChemAxon
polarizability 19.4 ChemAxon
药物相互作用
Drug Interaction
Calcium Formation of non-absorbable complexes
Calcium Acetate Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives such as alendronate. Avoid administration of oral calcium supplements within 30 minutes after alendronate.
Calcium Chloride Calcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 30 minutes after alendronate/risedronate.
Diclofenac Increased risk of gastric toxicity
Diflunisal Increased risk of gastric toxicity
Etodolac Increased risk of gastric toxicity
Fenoprofen Increased risk of gastric toxicity
Flurbiprofen Increased risk of gastric toxicity
Ibuprofen Increased risk of gastric toxicity
Indomethacin Increased risk of gastric toxicity
Iron Dextran Formation of non-absorbable complexes
Ketorolac Increased risk of gasrtic toxicity
Magnesium Formation of non-absorbable complexes
Mefenamic acid Increased risk of gastric toxicity
Nabumetone Increased risk of gastric toxicity
Naproxen Increased risk of gastric toxicity
Oxaprozin Increased risk of gastric toxicity
Oxyphenbutazone Increased risk of gastric toxicity
Piroxicam Increased risk of gastric toxicity
Tenoxicam Increased risk of gastric toxicity
食物相互作用
  • Take 30-60 minutes before breakfast.
  • Take with a full glass of water.

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