药品详细
Adefovir Dipivoxil(阿德福韦酯)
化学结构式图
中文名
阿德福韦酯
英文名
Adefovir Dipivoxil
分子式
C20H32N5O8P
化学名
[({[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}({[(2,2-dimethylpropanoyl)oxy]methoxy})phosphoryl)oxy]methyl 2,2-dimethylpropanoate
分子量
Average: 501.4705
Monoisotopic: 501.198849537
Monoisotopic: 501.198849537
CAS号
142340-99-6
ATC分类
J05A Direct acting antivirals
药物类型
small molecule
阶段
approved
商品名
Hepsera;Preveon;
同义名
Adefovir;adefovir dipivoxil;Adefovir pivoxil;Adefovirdipivoxl;ADV;bis-POM PMEA;GS-840;PMEA;
基本介绍
Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered nucleotide analog reverse transcriptase inhibitor (ntRTI) used for treatment of hepatitis B. It is a failed treatment for HIV. [Wikipedia]
生产厂家
- Gilead sciences inc
封装厂家
参考
Synthesis Reference | Not Available |
General Reference | Not Available |
剂型
规格
化合物类型
Type | small molecule |
Classes |
|
Substructures |
|
适应症
ANTIVIRALS 抗病毒;
药理
Indication | For the treatment of chronic hepatitis B 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 | Adefovir dipivoxil a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The concentration of adefovir that inhibited 50% of viral DNA synthesis (IC50) in vitro ranged from 0.2 to 2.5 μM in HBV transfected human hepatoma cell lines. The combination of adefovir with lamivudine showed additive anti-HBV activity. | ||||||
Mechanism of action | Adefovir dipivoxil is a prodrug of adefovir. Adefovir is an acyclic nucleotide analog of adenosine monophosphate which is phosphorylated to the active metabolite adefovir diphosphate by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. The inhibition constant (Ki) for adefovir diphosphate for HBV DNA polymerase was 0.1 μM. Adefovir diphosphate is a weak inhibitor of human DNA polymerases α and γ with Ki values of 1.18 μM and 0.97μM, respectively. | ||||||
Absorption | Approximate oral bioavailability is 59%. | ||||||
Volume of distribution |
|
||||||
Protein binding | ≤4% over the adefovir concentration range of 0.1 to 25 μg/mL | ||||||
Metabolism |
Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. Forty-five percent of the dose is recovered as adefovir in the urine over 24 hours at steady state following 10 mg oral doses. Adefovir is not a substrate of the cytochrome P450 enzymes.
|
||||||
Route of elimination | Adefovir is renally excreted by a combination of glomerular filtration and active tubular secretion. | ||||||
Half life | Terminal elimination half-life of 7.48 ± 1.65 hours | ||||||
Clearance |
|
||||||
Toxicity | Renal tubular nephropathy characterized by histological alterations and/or increases in BUN and serum creatinine was the primary dose-limiting toxicity associated with administration of adefovir dipivoxil in animals. Nephrotoxicity was observed in animals at systemic exposures approximately 3–10 times higher than those in humans at the recommended therapeutic dose of 10 mg/day. | ||||||
Affected organisms |
|
||||||
Pathways |
|
理化性质
Properties | |||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
State | solid | ||||||||||||||||||||||||||||||||||||||||||
Experimental Properties |
|
||||||||||||||||||||||||||||||||||||||||||
Predicted Properties |
|
药物相互作用
Drug | Interaction |
---|---|
Valganciclovir | The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Adefovir Dipivoxil, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended. |
食物相互作用
- Take without regard to meals.