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

Details

Stereochemistry ACHIRAL
Molecular Formula C20H32N5O8P
Molecular Weight 501.4705
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ADEFOVIR DIPIVOXIL

SMILES

CC(C)(C)C(=O)OCOP(=O)(COCCN1C=NC2=C1N=CN=C2N)OCOC(=O)C(C)(C)C

InChI

InChIKey=WOZSCQDILHKSGG-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C20H32N5O8P
Molecular Weight 501.4705
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

2002
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
Herpes simplex virus-specified DNA polymerase is the target for the antiviral action of 9-(2-phosphonylmethoxyethyl)adenine.
1991 Jan 5
Early therapy of feline leukemia virus infection (FeLV-FAIDS) with 9-(2-phosphonylmethoxyethyl)adenine (PMEA).
1991 Jul
9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo.
1991 Jun 1
Chemotherapy of feline immunodeficiency virus infection.
1991 Nov 15
Nickel(II), copper(II) and zinc(II) complexes of 9-[2- (phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA), the 8-aza derivative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl] adenine (PMEA). Quantification of four isomeric species in aqueous solution.
2004
6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity.
2004 Oct
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
Deoxythreosyl phosphonate nucleosides as selective anti-HIV agents.
2005 Apr 13
cycloSal-PMEA and cycloAmb-PMEA: potentially new phosphonate prodrugs based on the cycloSal-pronucleotide approach.
2005 Dec 15
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
Novel acyclic nucleoside phosphonate analogues with potent anti-hepatitis B virus activities.
2005 Mar
In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase.
2005 Mar
Susceptibilities of several clinical varicella-zoster virus (VZV) isolates and drug-resistant VZV strains to bicyclic furano pyrimidine nucleosides.
2005 Mar
Spectrum of antiviral activity of o-(acetoxyphenyl)hept-2-ynyl sulphide (APHS).
2005 May
Introduction to chronic hepatitis B infection.
2006
In vitro comparison of antiviral drugs against feline herpesvirus 1.
2006 Apr 26
Inhibition of human liver microsomal cytochrome P450 activities by adefovir and tenofovir.
2006 Dec
The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3.
2006 Dec
Synthesis, in vitro antiviral evaluation, and stability studies of novel alpha-borano-nucleotide analogues of 9-[2-(phosphonomethoxy)ethyl]adenine and (R)-9-[2-(phosphonomethoxy)propyl]adenine.
2006 Dec 28
Cellular and virological mechanisms of HBV drug resistance.
2006 Feb
Virologic response and resistance to adefovir in patients with chronic hepatitis B.
2006 Feb
Purine P1 receptor-dependent immunostimulatory effects of antiviral acyclic analogues of adenine and 2,6-diaminopurine.
2006 Jan 13
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
Favorable outcome of liver transplantation despite a high hepatitis B virus replication: beyond the limits?
2006 Sep
Decompensated lamivudine-resistant hepatitis B virus-related cirrhosis treated successfully with adefovir dipivoxil allowing surgery for hepatocellular carcinoma.
2007
Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection.
2007 Apr 6
Successful treatment of an entecavir-resistant hepatitis B virus variant.
2007 Dec
Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines.
2007 Jan
Design and synthesis of novel bis(L-amino acid) ester prodrugs of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) with improved anti-HBV activity.
2007 Jan 15
Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution.
2007 Jul 15
Redetection of HBV lamivudine-resistant mutations in a patient under entecavir therapy, who had been treated sequentially with nucleos(t)ide analogues.
2007 Nov
Some new acyclic nucleotide analogues as antiviral prodrugs: synthesis and bioactivities in vitro.
2007 Nov 15
Secretion of antiretroviral chemokines by human cells cultured with acyclic nucleoside phosphonates.
2007 Nov 21
In vitro drug susceptibility analysis of hepatitis B virus clinical quasispecies populations.
2007 Oct
Combination therapy in liver transplant recipients with hepatitis B virus without hepatitis B immune globulin.
2007 Oct
Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis.
2008 Aug
Prophylaxsis against recurrance of hepatitis B virus after liver transplantation: a retrospective analysis spanning 20 years.
2008 Jan
Living donor liver transplantation for hepatitis B associated liver diseases: a 10-year experience in a single center.
2008 Jul-Aug
The human multidrug resistance protein 4 (MRP4, ABCC4): functional analysis of a highly polymorphic gene.
2008 Jun
[Factors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients].
2008 Mar
Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B.
2008 Mar 21
Permeation enhancer dodecyl 6-(dimethylamino)hexanoate increases transdermal and topical delivery of adefovir: influence of pH, ion-pairing and skin species.
2008 Nov
Gene induction for the treatment of methylmalonic aciduria.
2009 Apr
Telbivudine, a nucleoside analog inhibitor of HBV polymerase, has a different in vitro cross-resistance profile than the nucleotide analog inhibitors adefovir and tenofovir.
2009 Feb
Renal side effects of adefovir in hepatitis B virus-(HBV) positive kidney allograft recipients.
2009 Jan
Association of lamivudine-resistant mutational patterns with the antiviral effect of adefovir in patients with chronic hepatitis B.
2009 Mar
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:48:29 GMT 2023
Edited
by admin
on Fri Dec 15 15:48:29 GMT 2023
Record UNII
U6Q8Z01514
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ADEFOVIR DIPIVOXIL
EMA EPAR   MART.   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
ADEFOVIR DIPIVOXIL [VANDF]
Common Name English
ADEFOVIR PIVOXIL [JAN]
Common Name English
GS-0840
Code English
PROPANOIC ACID, 2,2-DIMETHYL-, (((2-(6-AMINO-9H-PURIN-9-YL)ETHOXY)METHYL)PHOSPHINYLIDENE)BIS(OXYMETHYLENE) ESTER
Common Name English
HEPSERA
Brand Name English
ADEFOVIR DIPIVOXIL [MART.]
Common Name English
[[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid, diester with hydroxymethyl pivalate
Common Name English
ADEFOVIR DIPIVOXIL [EMA EPAR]
Common Name English
ADEFOVIR DIPIVOXIL [ORANGE BOOK]
Common Name English
Adefovir dipivoxil [WHO-DD]
Common Name English
ADEFOVIR DI(PIVALOYLOXYMETHYL) ESTER
MI  
Common Name English
9-(2-((BIS((PIVALOYLOXY)METHOXY)PHOSPHINYL)METHOXY)ETHYL)ADENINE
Systematic Name English
ADEFOVIR PIVOXIL
JAN  
Common Name English
ADEFOVIR DIPIVOXIL [USAN]
Common Name English
ADEFOVIR DI(PIVALOYLOXYMETHYL) ESTER [MI]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS HEPSERA (AUTHORIZED: HEPTATIS B, CHRONIC)
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
WHO-VATC QJ05AF08
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
WHO-ATC J05AF08
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
NCI_THESAURUS C97452
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
Code System Code Type Description
SMS_ID
100000093015
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
EVMPD
SUB12454MIG
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
EPA CompTox
DTXSID5046487
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
FDA UNII
U6Q8Z01514
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
DRUG BANK
DB00718
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
NCI_THESAURUS
C28811
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
USAN
HH-36
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
RXCUI
141400
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY RxNorm
DAILYMED
U6Q8Z01514
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
MESH
C106812
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
DRUG CENTRAL
88
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
MERCK INDEX
m1409
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY Merck Index
CHEBI
31175
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
ChEMBL
CHEMBL922
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
CAS
142340-99-6
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
PUBCHEM
60871
Created by admin on Fri Dec 15 15:48:29 GMT 2023 , Edited by admin on Fri Dec 15 15:48:29 GMT 2023
PRIMARY
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