Chemical Properties
Pale Brown Solid
Uses
Used as an antiviral
Definition
ChEBI: Adefovir is a member of the class of phosphonic acids that is methylphosphonic acid in which one of the methyl hydrogens has been replaced by a 2-(6-amino-9H-purin-9-yl)ethoxy group. An inhibitor of HIV-1 reverse transcriptase, the bis(t-butoxycarbonyloxymethyl) ester (dipivoxil ester) prodrug is used to treat chronic hepatitis B viral infection. It has a role as a HIV-1 reverse transcriptase inhibitor, a drug metabolite, an antiviral drug, a nephrotoxic agent and a DNA synthesis inhibitor. It is a member of 6-aminopurines, an ether and a member of phosphonic acids. It is functionally related to an adenine. It is a conjugate acid of an adefovir(1-).
Acquired resistance
It has a lower propensity to induce drug resistance than lamivudine.
Clinical trials of patients receiving 48 weeks of therapy
did not identify any cases of resistance. Longer courses
yield resistant strains of HBV with mutations in the DNA
polymerase gene; other rare variants of resistant strains have
been identified. Lamivudine-resistant strains of HBV retain
susceptibility to adefovir.
Pharmaceutical Applications
A nucleotide analog of adenosine monophosphate, administered
orally as its prodrug, adefovir dipivoxil.
Biochem/physiol Actions
Adefovir is an antiviral drug that after intracellular conversion to adefovir diphosphate inhibits hepatitis B virus (HBV) DNA polymerase (reverse transcriptase).
Pharmacokinetics
Oral absorption： c. 60%
Cmax 10 mg/kg oral： 18.4 ng/mL
Plasma half-life： c. 7.5 h.
Volume of distribution： 392 mL/kg
Plasma protein binding： Not known
The prodrug is metabolized to adefovir, which is excreted by the kidneys and therefore requires dose adjustment in patients with impaired renal function. It does not induce cytochrome P450 at standard doses and does not influence the metabolism or plasma concentrations of the other licensed medications used in the treatment of hepatitis B.
Clinical Use
Treatment of chronic hepatitis B virus infection in patients >12 years
of age
Side effects
It is generally well tolerated, with headache, pharyngitis,
abdominal pain and peripheral neuropathy being the most
common side effects. Nephrotoxicity has been observed in
some patients, with those receiving higher doses and longer
courses of therapy at greater risk. Exacerbation of hepatitis
has been reported in patients immediately following discontinuation
of treatment. Most exacerbations occur within 12
weeks of stopping therapy, and elevations of alanine aminotransferase
(ALT) up to 10 times the upper limit of normal
can be observed in over 25% of patients. Lactic acidosis has
been reported in a few patients and is an indication for immediate
discontinuation.
