Adefovir Dipivoxil

Các tên gọi khác (6 ) :

Adéfovir
Adefovir
Adefovir dipivoxil
Adefovir Pivoxil
Adefovirum
HePSera

antiviral agents, reverse transcriptase inhibitors

Thuốc Gốc

Small Molecule

CAS: 142340-99-6

ATC: J05AF08

ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com

CTHH: C₂₀H₃₂N₅O₈P

PTK: 501.4705

Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered acyclic nucleotide analog reverse transcriptase inhibitor (ntRTI) used for treatment of hepatitis B. It is ineffective against HIV-1. [Wikipedia] Adefovir dipivoxil is the diester prodrug of adefovir.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₀H₃₂N₅O₈P

Phân tử khối

501.4705

Monoisotopic mass

501.198849537

InChI

InChI=1S/C20H32N5O8P/c1-19(2,3)17(26)30-11-32-34(28,33-12-31-18(27)20(4,5)6)13-29-8-7-25-10-24-14-15(21)22-9-23-16(14)25/h9-10H,7-8,11-13H2,1-6H3,(H2,21,22,23)

InChI Key

InChIKey=WOZSCQDILHKSGG-UHFFFAOYSA-N

IUPAC Name

[({[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}({[(2,2-dimethylpropanoyl)oxy]methoxy})phosphoryl)oxy]methyl 2,2-dimethylpropanoate

Traditional IUPAC Name

({[2-(6-aminopurin-9-yl)ethoxy]methyl[(2,2-dimethylpropanoyl)oxy]methoxyphosphoryl}oxy)methyl 2,2-dimethylpropanoate

SMILES

CC(C)(C)C(=O)OCOP(=O)(COCCN1C=NC2=C(N)N=CN=C12)OCOC(=O)C(C)(C)C

Độ hòa tan

19 mg/mL at pH 2.0 and 0.4 mg/mL at pH 7.2.

logP

1.91

logS

-2.9

pKa (strongest acidic)

18.59

pKa (Strongest Basic)

5.13

PSA

166.98 Å²

Refractivity

119.99 m³·mol^-1

Polarizability

49 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Dược Lực Học : 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.

Cơ Chế Tác Dụng : Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered acyclic nucleotide analog reverse transcriptase inhibitor (ntRTI) used for treatment of hepatitis B. It is ineffective against HIV-1. [Wikipedia] Adefovir dipivoxil is the diester prodrug of adefovir. 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.

Dược Động Học :

▧ Absorption :
The approximate oral bioavailability of adefovir from HEPSERA is 59%. When a single oral 10 mg dose is given to chronic hepatitis B patients, the peak plasma concentration (Cmax) of adefovir was 18.4 ± 6.26 ng/mL. This occurred between 0.58 - 4 hours post dose (Tmax). The adefovir area under the plasma concentration-time curve (AUC0–∞) was 220 ± 70.0 ng∙h/mL. Food does not affect the exposure of adeforvir.
▧ Volume of Distribution :
* 392 ± 75 mL/kg [Vd at steady state, intravenous administration of 1.0 mg/kg/day] * 352 ± 9 mL/kg [Vd at steady state, intravenous administration of 3.0 mg/kg/day]
▧ 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. 45% 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 :
Plasma adefovir concentrations declined in a biexponential manner with a terminal elimination half-life of 7.48 ± 1.65 hours.
▧ Clearance :
* 469 ± 99.0 mL/min [Patients with Unimpaired renal Function receiving a 10 mg single dose] * 356 ± 85.6 mL/min [Patients with mild renal impairement receiving a 10 mg single dose] * 237 ± 118 mL/min [Patients with moderate renal impairement receiving a 10 mg single dose] * 91.7 ± 51.3 mL/min [Patients with severe renal impairement receiving a 10 mg single dose]

Độc Tính : 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.

Chỉ Định : 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.

Tương Tác Thuốc :

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.

Liều Lượng & Cách Dùng : Tablet - Oral - 10 mg

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Hepsera 10 mg tablet

Giá bán buôn : USD >30.32

Đơn vị tính : tablet

Nhà Sản Xuất

Công ty : The United Laboratories Ltd

Sản phẩm biệt dược : A Di Xian
Công ty : Fujian Guangsheng Tang

Sản phẩm biệt dược : A Gan Ding
Công ty : Cipla

Sản phẩm biệt dược : Adesera
Công ty : Sun Pharmaceutical Industries Ltd.

Sản phẩm biệt dược : Adfovir
Công ty : Changzheng-Xinkai

Sản phẩm biệt dược : Ailuwei
Công ty : Square

Sản phẩm biệt dược : Antiva
Công ty : Ivax

Sản phẩm biệt dược : Biovir
Công ty : Tianjin Institute of Pharmaceutical Research

Sản phẩm biệt dược : Dai Ding
Công ty : Lukang

Sản phẩm biệt dược : Dinghe
Công ty : Gilead Sciences, Inc.

Sản phẩm biệt dược : Hepsera
Công ty : Incepta

Sản phẩm biệt dược : Infovir
Công ty : Fovir Pharm

Sản phẩm biệt dược : Jiule
Công ty : Jiangsu TianShiLi BeiTe Pharmaceutical Co., Ltd.

Sản phẩm biệt dược : Lifuzhi
Công ty : Chia Tai Tianqing

Sản phẩm biệt dược : Ming Zheng
Công ty : Vidipha

Sản phẩm biệt dược : Nafasera
Công ty : Gilead Sciences, Inc.

Sản phẩm biệt dược : Preveon
Công ty : PMP

Sản phẩm biệt dược : Pymefovir
Công ty : SL Pharm

Sản phẩm biệt dược : Xinfunuo
Công ty : Qilu

Sản phẩm biệt dược : Yilaifen

Đóng gói

Công ty : A-S Medication Solutions LLC

Website : http://orders.a-smeds.com
Công ty : Excella GmbH

Website : http://www.excella-pharma-source.de
Công ty : Gilead Sciences Inc.

Website : http://www.gilead.com
Công ty : Patheon Inc.

Website : http://www.patheon.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00718

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=60871

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507520

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C11277

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D01655

ChemSpider

http://www.chemspider.com/Chemical-Structure.54855.html

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50038612

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/61958-0501-1

PharmGKB

http://www.pharmgkb.org/drug/PA10005

Wikipedia

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

RxList

http://www.rxlist.com/cgi/generic3/hepsera.htm

Drugs.com

http://www.drugs.com/cdi/adefovir.html

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