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Abacavir is a guanosine analog that competitively inhibits the reverse transcriptase of the human immunodefiency virus (HIV) and is used in combination antiretroviral therapy for the treatment of HIV. It was approved by the US Food and Drug Administration in 1998 and has been in clinical use since that time. Abacavir is currently most commonly used as part of a fixed-dose combination, 600 mg in combination with lamivudine 300 mg which is given once-daily as part of combination antiretroviral therapy. It is also available as a liquid formulation and has been approved for use in children. Abacavir is well absorbed with an absolute bioavailability of 83% and can be taken without regard to food . Although the parent drug has a short plasma half-life of only 2 h, abacavir is metabolized to carbovir triphosphate which has an intracellular half-life of 20 h or longer [1, 2]. It is this long intracellular half-life of carbovir triphosphate that makes abacavir pharmacokinetically amenable to once-daily dosing and this has been supported by clinical data [3, 4]. Unlike other nucleoside analog reverse transcriptase inhibitors, abacavir is metabolized predominantly by the liver by two major pathways: alcohol dehydrogenase and uridine diphosphate glucruonyltransferase. Less than 2% is excreted unchanged in the urine . In addition, unlike other antiretroviral drugs that are metabolized by the liver such as nonnucleoside reverse transcriptase inhibitors and protease inhibitors, abacavir is not significantly metabolized by cytochrome (CYP) P450 enzymes. It also does not inhibit or induce CYP enzymes which make drug interactions unlikely. Therapeutic drug monitoring has been infrequently employed for abacavir as it is the intracellular concentrations of carbovir triphosphate which would be most likely to be associated with drug effect and these are difficult and costly to measure on a routine basis. There is also very little information on validated intracellular target concentrations and their association with clinical efficacy.
|Publication Type:||Book Chapter|
|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
|Copyright:||2011 Springer Science + Business Media, LLC|
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