| Item |
Information |
|
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 |
| • |
Human Immunodeficiency Virus |
|
| 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 |
| • |
Zucman D, Truchis P, Majerholc C, Stegman S, Caillat-Zucman S: Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population. J Acquir Immune Defic Syndr. 2007 May 1;45(1):1-3.
[Pubmed]
|
|
| External Links |
|