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药品详细

Entecavir (恩替卡韦 )

化学结构式图
中文名
恩替卡韦
英文名
Entecavir
分子式
Not Available
化学名
2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-6,9-dihydro-3H-purin-6-one
分子量
Average: 277.2792
Monoisotopic: 277.117489371
CAS号
142217-69-4
ATC分类
J05A Direct acting antivirals
药物类型
small molecule
阶段
商品名
Baraclude;
同义名
entecavir;
基本介绍

Entecavir is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade name Baraclude (BMS).

Entecavir is a guanine analogue that inhibits all three steps in the viral replication process, and the manufacturer claims that it is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir). It was approved by the U.S. Food and Drug Administration (FDA) in March 2005.

生产厂家
  • Bristol myers squibb
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
Form Route Strength
Tablet Oral
规格
Unit description Cost Unit
Baraclude 0.5 mg tablet 28.94 USD tablet
Baraclude 1 mg tablet 28.94 USD tablet
化合物类型
Type small molecule
Classes
  • Hypoxanthines
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
  • Hypoxanthines
适应症
ANTIVIRALS 抗病毒;
药理
Indication For the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Pharmacodynamics Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It is designed to selectively inhibit the Hepatitis B virus, blocking all three steps in the replication process. Entecavir is more efficient than an older Hepatitis B drug, lamivudine.
Mechanism of action By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity.
Absorption Absorption Following oral administration in healthy subjects, entecavir peak plasma concentrations occurred between 0.5 and 1.5 hours. In healthy subjects, the bioavailability of the tablet is 100% relative to the oral solution.
Volume of distribution Not Available
Protein binding Binding of entecavir to human serum proteins in vitro is approximately 13%.
Metabolism

Entecavir is not a substrate, inhibitor, or inducer of the cytochrome P450 (CYP450) enzyme system. Entecavir is efficiently phosphorylated to the active triphosphate form.
Route of elimination Not Available
Half life After reaching peak concentration, entecavir plasma concentrations decreased in a bi-exponential manner with a terminal elimination half-life of approximately 128-149 hours. The phosphorylated metabolite has a half-life of 15 hours.
Clearance
  • renal cl=383.2 +/- 101.8 mL/min [Unimpaired renal function]
  • renal cl=197.9 +/- 78.1 mL/min [Mild impaired renal function]
  • renal cl=135.6 +/- 31.6 mL/min [Moderate impaired renal function]
  • renal cl=40.3 +/- 10.1 mL/min [severe impaired renal function]
  • apparent oral cl=588.1 +/- 153.7 mL/min [Unimpaired renal function]
  • apparent oral cl=309.2 +/- 62.6 mL/min [Mild impaired renal function]
  • apparent oral cl=226.3 +/- 60.1 mL/min [Moderate impaired renal function]
  • apparent oral cl=100.6 +/- 29.1 mL/min [severe impaired renal function]
  • apparent oral cl=50.6 +/- 16.5 mL/min [severe impaired renal function amnaged with Hemodialysis]
  • apparent oral cl=35.7 +/- 19.6 mL/min [severe impaired renal function amnaged with CAPD]
Toxicity Healthy subjects who received single entecavir doses up to 40 mg or multiple doses up to 20 mg/day for up to 14 days had no increase in or unexpected adverse events. If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.
Affected organisms
  • Hepatitis B virus
Pathways Not Available
理化性质
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Slightly soluble (2.4 mg/mL at pH 7.9, 25oC) PhysProp
logP -0.8 PhysProp
Predicted Properties
Property Value Source
water solubility 6.59e+00 g/l ALOGPS
logP -0.81 ALOGPS
logP -1.44 ChemAxon Molconvert
logS -1.62 ALOGPS
pKa 14.64 ChemAxon Molconvert
hydrogen acceptor count 7 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 125.76 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 71.00 ChemAxon Molconvert
polarizability 27.31 ChemAxon Molconvert
药物相互作用
食物相互作用
  • Take on an empty stomach.
  • Taking the product with a high-fat meal or a light snack reduces the maximal concentration by 44 to 46% and total exposure by 18 to 20%.

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