| Indication |
For the treatment of HIV-1 infection, in combination with other antiretroviral agents. |
| Pharmacodynamics |
Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI)
with activity against Human Immunodeficiency Virus Type 1 (HIV-1).
Abacavir is phosphorylated to active metabolites that compete for
incorporation into viral DNA. They inhibit the HIV reverse transcriptase
enzyme competitively and act as a chain terminator of DNA synthesis.
The lack of a 3'-OH group in the incorporated nucleoside analogue
prevents the formation of the 5' to 3' phosphodiester linkage essential
for DNA chain elongation, and therefore, the viral DNA growth is
terminated. |
| Mechanism of action |
Abacavir is a carbocyclic synthetic nucleoside analogue.
Intracellularly, abacavir is converted by cellular enzymes to the active
metabolite carbovir triphosphate, an analogue of
deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits
the activity of HIV-1 reverse transcriptase (RT) both by competing with
the natural substrate dGTP and by its incorporation into viral DNA. |
| Absorption |
Rapid and extensive after oral administration (83% bioavailability) |
| Volume of distribution |
|
| Protein binding |
Moderate (approximately 50%)
|
| Metabolism |
Hepatic, by alcohol dehydrogenase and glucuronosyltransferase to
a 5′-carboxylic acid metabolite and 5′-glucuronide metabolite,
respectively. These metabolites have no antiviral activity. Abacavir is
not significantly metabolized by cytochrome P450 enzymes. |
| Route of elimination |
Elimination of abacavir was quantified in a mass balance study
following administration of a 600-mg dose of 14C-abacavir: 99% of the
radioactivity was recovered, 1.2% was excreted in the urine as abacavir,
30% as the 5′-carboxylic acid metabolite, 36% as the 5′-glucuronide
metabolite, and 15% as unidentified minor metabolites in the urine.
Fecal elimination accounted for 16% of the dose. Fecal elimination
accounted for 16% of the dose. Renal excretion of unchanged abacavir is a
minor route of elimination in humans. |
| Half life |
1.54 ± 0.63 hours |
| Clearance |
- 0.80 +/- 0.24 L/hr/kg [asymptomatic, HIV-1-infected adult patients receiving single (IV dose of 150 mg]
|
| Toxicity |
Some myocardial degeneration has been noticed in rats and mice |
