Adefovir

Structural formula
General
Non-proprietary name	Adefovir
other names	[2- (6-Amino-9 H -purin-9-yl) ethoxy] methylphosphonic acid ( IUPAC )
Molecular formula	C 8 H 12 N 5 O 4 P
External identifiers / databases
EC number	600-789-7
ECHA InfoCard	100.106.235
PubChem	60172
ChemSpider	54252
DrugBank	DB13868
Wikidata	Q353551
Drug information
ATC code	J05 AF08
Drug class	Antivirals
Mechanism of action	Nucleosidic Reverse Transcriptase Inhibitors
properties
Molar mass	273,19 g · mol -1
Melting point	> 260 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302-312-332
	P: 280
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Adefovir is an antiviral , the hepadnaviruses inhibits and therefore as a drug in the treatment of chronic hepatitis B is used. Chemically it is a nucleotide - analogue of adenine that with the natural due to its structural similarity substrate in its place in the viral DNA is incorporated and inhibits the proliferation as a result of hepatitis B virus (HBV). Lowering the viral load reduces liver damage.

Use as a medicine

Adefovir was approved in the US in 2002 and in the EU in 2003 in the form of its ester adefovir dipivoxil for the treatment of chronic hepatitis B in adults with decompensated liver disease or with compensated liver disease when they have certain findings, such as increased alanine aminotransferase -Serum values, active liver inflammation or liver fibrosis and proven active virus replication .

Mechanism of action

Adefovir Dipivoxil is a prodrug . After absorption, the nucleotide analogue adefovir, which is structurally related to adenosine monophosphate, is formed , which is phosphorylated in virus-infected cells to form active adefovir diphosphate. In nucleic acid synthesis, this competes with the natural substrate deoxyadenosine triphosphate and inactivates the viral DNA polymerase ( "suicide inhibition" ). Nucleotides built into the DNA also prevent the attachment of further nucleotides due to their chemical structure and the chain is broken. For an antiviral effect, comparatively low adefovir concentrations, which do not inhibit the human DNA polymerases, are sufficient.

Clinical resistance to adefovir can arise from point mutations in the HBV polymerase gene, but the observed increase in resistance was small.

Pharmacokinetics

The oral bioavailability of adefovir dipivoxil is approximately 60% and the conversion to adefovir is rapid. Plasma protein binding is low (<4%). The potential for cytochrome P450 -mediated interactions between adefovir and other medicinal products is considered to be low. Adefovir is excreted unchanged by the kidneys by both glomerular filtration and active tubular secretion. The plasma levels fall bi- exponentially , the median of the plasma half-life is around 7 hours.

Side effects and restrictions on use

The dose of adefovir is limited by its nephrotoxicity . Renal function must be monitored and the dosage should be adjusted if a restriction is found. Hepsera is not recommended for use in adolescents under 18 years of age, and there is no dose recommendation for patients over 65 years of age. Due to insufficient data, the risk-benefit assessment in pregnancy should be carried out accordingly. As it is not known whether adefovir is excreted in breast milk, patients should refrain from breastfeeding while taking adefovir dipivoxil. In addition to nephrotoxic effects, gastrointestinal complaints and headaches can mainly occur.

Trade names

Adefovir is commercially available in Germany, Austria and Switzerland under the name Hepsera.

Web links

Public Assessment Report (EPAR) from the European Medicines Agency (EMA) for: Adefovir

Individual evidence

^ Entry on adefovir. In: Römpp Online . Georg Thieme Verlag, accessed on November 10, 2014.

↑ ^a ^b Data sheet adefovir dipivoxil from Sigma-Aldrich , accessed on March 20, 2011 ( PDF ).

↑ External identifiers or database links for adefovir dipivoxil : CAS number: 142340-99-6, EC number: 634-317-6, ECHA InfoCard: 100.162.308 , PubChem : 60871 , DrugBank : DB00718 , Wikidata : Q28851735 .

^ ^A ^b Ernst Mutschler, Gerd Geisslinger, Heyo K. Kroemer, Peter Ruth, Monika Schäfer-Korting: drug effects. Textbook of pharmacology and toxicology. 9th edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 2008, ISBN 978-3-8047-1952-1 .

↑ ^a ^b ^c ^d ^e Hepsera: Summary of the Product Characteristics, Status: January 2009 (PDF; 456 kB) on the website of the European Medicines Agency (EMEA).

↑ ROTE LISTE 2017, Verlag Rote Liste Service GmbH, Frankfurt am Main, ISBN 978-3-946057-10-9 , p. 158.

↑ Swiss Medicines Compendium , as of August 2009.

↑ AGES-PharmMed, as of August 2009.

[RÖMPP_Online-1] Entry on adefovir. In: Römpp Online . Georg Thieme Verlag, accessed on November 10, 2014.

[Sigma-2] Data sheet adefovir dipivoxil from Sigma-Aldrich , accessed on March 20, 2011 ( PDF ).

[3] External identifiers or database links for adefovir dipivoxil : CAS number: 142340-99-6, EC number: 634-317-6, ECHA InfoCard: 100.162.308 , PubChem : 60871 , DrugBank : DB00718 , Wikidata : Q28851735 .

[mutschler-4] A ^b Ernst Mutschler, Gerd Geisslinger, Heyo K. Kroemer, Peter Ruth, Monika Schäfer-Korting: drug effects. Textbook of pharmacology and toxicology. 9th edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 2008, ISBN 978-3-8047-1952-1 .