Abacavir is a carbocyclic 2'-deoxyguanosine nucleoside reverse transcriptase inhibitor that is used as either a 600-mg once-daily or 300-mg twice-daily regimen exclusively in the treatment of HIV infection. Abacavir is rapidly absorbed after oral administration, with peak concentrations occurring 0.63-1 hour after dosing. The absolute bioavailability of abacavir is approximately 83%. Abacavir pharmacokinetics are linear and dose-proportional over the range of 300-1200 mg/day. To date, one study has assessed the steady-state pharmacokinetics of abacavir following a 600-mg once-daily regimen, and reported a geometric mean steady-state abacavir peak concentration of 3.85 microg/mL. Although this concentration is higher than the steady-state abacavir peak concentration reported following a 300-mg twice-daily regimen (0.88-3.19 microg/mL, depending on the study), the geometric mean steady-state abacavir exposure over 24 hours was similar following these regimens. Coadministration with food has no significant effect on abacavir exposure; therefore, abacavir may be administered with or without food.The apparent volume of distribution of abacavir after intravenous administration is approximately 0.86 +/- 0.15 L/kg, suggesting that abacavir is distributed to extravascular spaces. Binding to plasma proteins is about 50% and is independent of the plasma abacavir concentration. Abacavir is extensively metabolized by the liver; less than 2% is excreted as unchanged drug in the urine. Abacavir is primarily metabolized via two pathways, uridine diphosphate glucuronyltransferase and alcohol dehydrogenase, resulting in the inactive glucuronide metabolite (361W94, ~36% of the dose recovered in the urine) and the inactive carboxylate metabolite (2269W93, approximately 30% of the dose recovered in the urine). The remaining 15% of abacavir equivalents found in the urine are minor metabolites, each less than 2% of the total dose. Faecal elimination accounts for about 16% of the dose. The terminal elimination half-life of abacavir is approximately 1.5 hours. The antiviral effect of abacavir is due to its intracellular anabolite, carbovir-triphosphate (CBV-TP). When assessed by validated high-performance liquid chromatography electrospray ionization tandem mass spectrometry, CBV-TP has been shown to have a long elimination half-life (>20 hours), supporting once-daily dosing. The mean CBV-TP trough concentrations do not differ following abacavir 600-mg once-daily and 300-mg twice-daily regimens. Limited data are available for abacavir in subjects with renal dysfunction or hepatic impairment. Abacavir pharmacokinetics in HIV-infected subjects with end-stage renal disease were found to be no different from those observed in healthy adults; this finding was consistent with the kidney being a minor route of abacavir elimination. A study of abacavir pharmacokinetics in hepatically impaired adults (Child-Pugh score of 5-6) showed that the abacavir area under the plasma concentration-time curve and elimination half-life were 89% and 58% greater, respectively, suggesting that the daily dose of abacavir should be reduced in patients with mild hepatic impairment (Child-Pugh score of 5-6). Abacavir pharmacokinetics have not been studied in patients with higher Child-Pugh scores. Abacavir is not significantly metabolized by cytochrome P450 (CYP) enzymes, nor does it inhibit these enzymes. Therefore, clinically significant drug interactions between abacavir and drugs metabolized by CYP enzymes are unlikely. The potential for drug interactions is no different when abacavir is used as a once-daily regimen versus a twice-daily regimen. No clinically significant drug interactions have been observed between recommended doses of abacavir and lamivudine, zidovudine, alcohol (ethanol) or methadone.