化合物信息

Drug Groups

approved; investigational

Description

Abacavir (ABC) is a powerful nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. [Wikipedia]

Indication

For the treatment of HIV-1 infection, in combination with other antiretroviral agents.

Pharmacology

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.

Toxicity

Some myocardial degeneration has been noticed in rats and mice

Affected Organisms

Biotransformation

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.

Absorption

Rapid and extensive after oral administration (83% bioavailability)

Half Life

1.54 ± 0.63 hours

Protein Binding

Moderate (approximately 50%)

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.

Distribution

* 0.86 ± 0.15 L/kg

Clearance

* 0.80 +/- 0.24 L/hr/kg [asymptomatic, HIV-1-infected adult patients receiving single (IV dose of 150?mg]

References

External Links