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Details

Stereochemistry ACHIRAL
Molecular Formula C20H32N5O8P
Molecular Weight 501.4713
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)(COCCn1cnc2c(N)ncnc21)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 501.4713
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: http://link.springer.com/chapter/10.1007%2F978-0-387-49785-3_33

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

1032480000000
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
Health Status: unhealthy
Age Group: 12 - 17 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 2 - 6 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 7 - 11 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 12 - 17 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 12 - 17 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 12 - 17 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 7 - 11 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 7 - 11 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 7 - 11 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 7 - 11 years
Sex: M+F
Sources:
Overview

OverviewOther

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Herpes simplex virus-specified DNA polymerase is the target for the antiviral action of 9-(2-phosphonylmethoxyethyl)adenine.
1991 Jan 5
In vitro selection and molecular characterization of human immunodeficiency virus-1 resistant to non-nucleoside inhibitors of reverse transcriptase.
1992 Mar
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
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
Acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents.
2001 Apr-Jul
Cross-resistance testing of antihepadnaviral compounds using novel recombinant baculoviruses which encode drug-resistant strains of hepatitis B virus.
2001 Jun
Prevention and inhibition of nasopharyngeal carcinoma growth by antiviral phosphonated nucleoside analogs.
2001 Nov 1
Design, synthesis, and biological evaluation of novel nucleoside and nucleotide analogues as agents against DNA viruses and/or retroviruses.
2001 Oct 25
In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.
2001 Sep
Raman spectroscopy study of acid-base and structural properties of 9-[2-(phosphonomethoxy)ethyl]adenine in aqueous solutions.
2002
Antiretrovirus activity of a novel class of acyclic pyrimidine nucleoside phosphonates.
2002 Jul
Antiviral activities of MCC-478, a novel and specific inhibitor of hepatitis B virus.
2002 Sep
In vitro activity of potential anti-poxvirus agents.
2003 Jan
Phosphorothioate di- and trinucleotides as a novel class of anti-hepatitis B virus agents.
2004 Jun
Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2-(phosphonomethoxy)ethoxy]pyrimidine and related compounds.
2004 Jun 15
6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity.
2004 Oct
Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro.
2004 Oct
Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV.
2005
cycloSal-PMEA and cycloAmb-PMEA: potentially new phosphonate prodrugs based on the cycloSal-pronucleotide approach.
2005 Dec 15
Novel acyclic nucleoside phosphonate analogues with potent anti-hepatitis B virus activities.
2005 Mar
Introduction to chronic hepatitis B infection.
2006
Inhibition of human liver microsomal cytochrome P450 activities by adefovir and tenofovir.
2006 Dec
Cellular and virological mechanisms of HBV drug resistance.
2006 Feb
Purine P1 receptor-dependent immunostimulatory effects of antiviral acyclic analogues of adenine and 2,6-diaminopurine.
2006 Jan 13
Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution.
2007 Jul 15
Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis.
2008 Aug
The human multidrug resistance protein 4 (MRP4, ABCC4): functional analysis of a highly polymorphic gene.
2008 Jun
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 Sat Jun 26 00:43:15 UTC 2021
Edited
by admin
on Sat Jun 26 00:43:15 UTC 2021
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
ADEFOVIR DIPIVOXIL [WHO-DD]
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 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 Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
WHO-VATC QJ05AF08
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
WHO-ATC J05AF08
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
NCI_THESAURUS C97452
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
Code System Code Type Description
EVMPD
SUB12454MIG
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
EPA CompTox
142340-99-6
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
FDA UNII
U6Q8Z01514
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
DRUG BANK
DB00718
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
NCI_THESAURUS
C28811
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
RXCUI
141400
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY RxNorm
MESH
C106812
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
DRUG CENTRAL
88
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
MERCK INDEX
M1409
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL922
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
CAS
142340-99-6
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
PUBCHEM
60871
Created by admin on Sat Jun 26 00:43:15 UTC 2021 , Edited by admin on Sat Jun 26 00:43:15 UTC 2021
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
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