Coadministration of zidovudine with abacavir produced a small and inconsistent effect on abacavir pharmacokinetic parameters across the different doses. At steady state, abacavir pharmacokinetic parameters (area under the plasma concentration-time curve for a dosing interval and peak concentration ) were generally proportional to dose over the range of a 600- to 1,200-mg total daily dose. Steady-state plasma abacavir concentrations were achieved by week 4 of monotherapy and persisted to week 12. The concentrations of abacavir in cerebrospinal fluid were determined in a subset of subjects. Pharmacokinetic parameters were calculated for abacavir after administration of the first dose and at week 4 and for abacavir, zidovudine, and its glucuronide metabolite at week 12. Seventy-nine subjects received abacavir monotherapy for 4 weeks (200, 400, or 600 mg every 8 hours and 300 mg every 12 h ) and thereafter received either zidovudine (200 mg TID or 300 mg BID) or matching placebo with abacavir for 8 additional weeks. The present study was conducted to determine the multiple-dose pharmacokinetics and pharmacodynamics of abacavir in HIV-1-infected subjects following oral administration of daily doses that ranged from 600 to 1,800 mg, with and without zidovudine. Abacavir (1592U89) is a nucleoside reverse transcriptase inhibitor with potent activity against human immunodeficiency virus type 1 (HIV-1) when used alone or in combination with other antiretroviral agents.