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Fluconazole pharmacokinetics, including absolute bioavailability, were determined for one group of controls (n = 10) and two groups of people with human immunodeficiency virus (HIV) infection (those with CD4+ T-cell counts of less than [n = 4] or greater than [n = 9] 200 cells per mm3). Twenty subjects received four doses of fluconazole; three doses were oral (50, 100, and 400 mg), and one dose was intravenous (either 50, 100, or 400 mg). The other three subjects received one or two doses. The groups were comparable in terms of the weight, body mass index, and estimated creatinine clearance of the subjects, but the people with HIV infection were older. Pharmacokinetic parameters indicated linearity in all subjects; the area under the plasma concentration-time curve and the maximum concentration increased in proportion to the dose. The fraction of an oral dose of fluconazole absorbed approximated unity in all three groups of subjects. The mean (+/- standard deviation) plasma clearance of fluconazole was lowest in the group of subjects with low CD4+ T-cell counts; the value for this group was 0.74 +/- 0.19 liter/h, compared with 0.97 +/- 0.19 liter/h in the group with HIV infection and CD4+ T-cell counts of greater than 200 cells/mm3 and 1.18 +/- 0.23 liter/h in the group of control subjects (P &lt; 0.05). The volume of distribution was lower in those with HIV infection (P = 0.04, corrected for weight). The half-life was longest in people with HIV infection and low CD4+ T-cell counts (P = 0.01). This study has shown that some differences do exist between the pharmacokinetics of fluconazole in people with HIV infection and those in noninfected controls.

antimicrobial agents and chemotherapy

Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection