U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C8H12N5O4P
Molecular Weight 273.1857
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ADEFOVIR

SMILES

NC1=NC=NC2=C1N=CN2CCOCP(O)(O)=O

InChI

InChIKey=SUPKOOSCJHTBAH-UHFFFAOYSA-N
InChI=1S/C8H12N5O4P/c9-7-6-8(11-3-10-7)13(4-12-6)1-2-17-5-18(14,15)16/h3-4H,1-2,5H2,(H2,9,10,11)(H2,14,15,16)

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/14498759 http://link.springer.com/chapter/10.1007%2F978-0-387-49785-3_33

The potential antiviral effect of adefovir, an acyclic nucleoside phosphonate analog of 2′-deoxyadenosine monophosphate, was first studied by Holý and De Clercq in 1980s. 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. Oral adefovir dipivoxil is effective and generally well tolerated in HBeAg-positive and -negative patients chronically infected with wild-type or lamivudine-resistant HBV.

Originator

Curator's Comment: (De Clercq et al., 1986, 1987; Holý et al., 1999, 2002)

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
HEPSERA

Approved Use

HEPSERA is indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histological, virological, biochemical, and serological responses in adult patients with HBeAg+ and HBeAg- chronic hepatitis B with compensated liver function, and with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function. For patients 12 to <18 years of age, the indication is based on virological and biochemical responses in patients with HBeAg+ chronic hepatitis B virus infection with compensated liver function. HEPSERA is a nucleotide analogue indicated for the treatment of chronic hepatitis B in patients ≥12 years of age. (1)

Launch Date

1.03248003E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
18.4 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ADEFOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
220 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ADEFOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.48 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ADEFOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
96%
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ADEFOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
10 mg 1 times / day multiple, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 12 - 17 years
n = 15
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 12 - 17 years
Sex: M+F
Population Size: 15
Sources:
Other AEs: Rhinorrhea, Sneezing...
Other AEs:
Rhinorrhea (1 patient)
Sneezing (1 patient)
Blister (1 patient)
Sources:
0.3 mg/kg 1 times / day multiple, oral
Recommended
Dose: 0.3 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.3 mg/kg, 1 times / day
Sources:
unhealthy, 2 - 6 years
n = 13
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 2 - 6 years
Sex: M+F
Population Size: 13
Sources:
0.3 mg/kg 1 times / day multiple, oral
Recommended
Dose: 0.3 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.3 mg/kg, 1 times / day
Sources:
unhealthy, 7 - 11 years
n = 19
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 7 - 11 years
Sex: M+F
Population Size: 19
Sources:
Other AEs: Headache, Vertigo...
Other AEs:
Headache (1 patient)
Vertigo (1 patient)
Disturbance in attention (1 patient)
Disorder eye (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Blister 1 patient
10 mg 1 times / day multiple, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 12 - 17 years
n = 15
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 12 - 17 years
Sex: M+F
Population Size: 15
Sources:
Rhinorrhea 1 patient
10 mg 1 times / day multiple, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 12 - 17 years
n = 15
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 12 - 17 years
Sex: M+F
Population Size: 15
Sources:
Sneezing 1 patient
10 mg 1 times / day multiple, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 12 - 17 years
n = 15
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 12 - 17 years
Sex: M+F
Population Size: 15
Sources:
Disorder eye 1 patient
0.3 mg/kg 1 times / day multiple, oral
Recommended
Dose: 0.3 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.3 mg/kg, 1 times / day
Sources:
unhealthy, 7 - 11 years
n = 19
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 7 - 11 years
Sex: M+F
Population Size: 19
Sources:
Disturbance in attention 1 patient
0.3 mg/kg 1 times / day multiple, oral
Recommended
Dose: 0.3 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.3 mg/kg, 1 times / day
Sources:
unhealthy, 7 - 11 years
n = 19
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 7 - 11 years
Sex: M+F
Population Size: 19
Sources:
Headache 1 patient
0.3 mg/kg 1 times / day multiple, oral
Recommended
Dose: 0.3 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.3 mg/kg, 1 times / day
Sources:
unhealthy, 7 - 11 years
n = 19
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 7 - 11 years
Sex: M+F
Population Size: 19
Sources:
Vertigo 1 patient
0.3 mg/kg 1 times / day multiple, oral
Recommended
Dose: 0.3 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.3 mg/kg, 1 times / day
Sources:
unhealthy, 7 - 11 years
n = 19
Health Status: unhealthy
Condition: chronic hepatitis B
Age Group: 7 - 11 years
Sex: M+F
Population Size: 19
Sources:
Overview

OverviewOther

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound.
1991 Feb 15
Susceptibility of lamivudine-resistant hepatitis B virus to other reverse transcriptase inhibitors.
1999 Jun
In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine.
2000 Jul
In vivo anti-papillomavirus activity of nucleoside analogues including cidofovir on CRPV-induced rabbit papillomas.
2000 Nov
A new acyclic heterodinucleotide active against human immunodeficiency virus and herpes simplex virus.
2000 Sep
Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA.
2001 Apr 23
Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir.
2001 Dec
Intramolecular stacking interactions in ternary copper(II) complexes formed with 2,2'-bipyridine or 1,10-phenanthroline and 9-(4-phosphonobutyl)adenine (dPMEA), the carba relative of the antiviral nucleotide analogue 9.
2001 Mar
6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activity.
2002 Apr 25
Novel nucleoside analogue MCC-478 (LY582563) is effective against wild-type or lamivudine-resistant hepatitis B virus.
2002 Aug
Intramolecular stacking interactions in ternary copper(II) complexes formed by a heteroaromatic amine and 9-[2-(2-phosphonoethoxy)ethyl]adenine, a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine.
2004 Dec
Quantification of isomeric equilibria formed by metal ion complexes of 8-[2-(phosphonomethoxy)ethyl]-8-azaadenine (8,8aPMEA) and 9-[2-(phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA). Derivatives of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA).
2004 Dec
Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action.
2004 Mar 30
Antiviral potential of a new generation of acyclic nucleoside phosphonates, the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines.
2005
Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV.
2005
Acid-base and metal-ion-binding properties of 9-[2-(2-phosphonoethoxy)ethyl]adenine (PEEA), a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). An exercise on the quantification of isomeric complex equilibria in solution.
2005 Jul 11
Inhibition of human liver microsomal cytochrome P450 activities by adefovir and tenofovir.
2006 Dec
In vivo effects of antiviral acyclic nucleoside phosphonate 9-[2-(phosphonomethoxy)ethyl]adenine (adefovir) on cytochrome P450 system of rat liver microsomes.
2006 May
Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy.
2006 Nov
Synthesis and antiviral evaluation of alkoxyalkyl esters of acyclic purine and pyrimidine nucleoside phosphonates against HIV-1 in vitro.
2006 Oct
Decompensated lamivudine-resistant hepatitis B virus-related cirrhosis treated successfully with adefovir dipivoxil allowing surgery for hepatocellular carcinoma.
2007
Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution.
2007 Jul 15
Prophylaxsis against recurrance of hepatitis B virus after liver transplantation: a retrospective analysis spanning 20 years.
2008 Jan
Renal side effects of adefovir in hepatitis B virus-(HBV) positive kidney allograft recipients.
2009 Jan
Patents

Sample Use Guides

One tablet containing 10 mg adefovir dipivoxil once daily orally
Route of Administration: Oral
The concentration of adefovir that inhibited 50% of viral DNA synthesis (EC50) in HBV transfected human hepatoma cell lines ranged from 0.2 to 2.5 uM.
Name Type Language
ADEFOVIR
INN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
adefovir [INN]
Common Name English
ADEFOVIR [VANDF]
Common Name English
GS0393
Code English
ADEFOVIR [USAN]
Common Name English
[[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid
Systematic Name English
PHOSPHONIC ACID, ((2-(6-AMINO-9H-PURIN-9-YL)ETHOXY)METHYL)-
Common Name English
Adefovir [WHO-DD]
Common Name English
PMEA
Common Name English
GS-0393
Code English
9-(2-(PHOSPHONOMETHOXY)ETHYL)ADENINE
Systematic Name English
ADEFOVIR [MI]
Common Name English
9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE
Common Name English
ADEFOVIR [MART.]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175459
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
NDF-RT N0000175459
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
NCI_THESAURUS C97452
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
LIVERTOX NBK548633
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
NDF-RT N0000175656
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
NDF-RT N0000009947
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
NDF-RT N0000175459
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
Code System Code Type Description
CHEBI
134512
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
INN
7313
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
ChEMBL
CHEMBL484
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
NCI_THESAURUS
C61526
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
MERCK INDEX
m1409
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY Merck Index
DAILYMED
6GQP90I798
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
FDA UNII
6GQP90I798
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
EPA CompTox
DTXSID6046214
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
CAS
106941-25-7
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
RXCUI
16521
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY RxNorm
MESH
C053001
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
LACTMED
Adefovir
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
SMS_ID
100000090470
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
USAN
GG-19
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
PUBCHEM
60172
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
EVMPD
SUB05264MIG
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
WIKIPEDIA
Adefovir
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
DRUG BANK
DB13868
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
HSDB
8079
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY
CHEBI
2469
Created by admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
PRIMARY