Following either single- or multiple oral doses for up to 14 days, fluconazole penetrates into all body fluids studied (see table below). Plasma protein binding is low (11 to 12%). The apparent volume of distribution of fluconazole approximates that of total body water.
Administration of a loading dose (on Day 1) of twice the usual daily dose results in plasma concentrations close to steady-state by the second day.
Steady-state concentrations are reached within 5 to 10 days following oral doses of 50 to 400 mg given once daily. Therefore, fluconazole may be taken without regard to meals (See Maxand AUC data from a food-effect study involving administration of fluconazole tablets to healthy volunteers under fasting conditions and with a high-fat meal indicated that exposure to the drug is not affected by food. Maxof 6.72 mcg/mL (range: 4.12 to 8.08 mcg/mL) and after single oral doses of 50 to 400 mg, fluconazole plasma concentrations and area under the plasma concentration-time curve (AUC) are dose proportional. In fasted normal volunteers, administration of a single oral 400 mg dose of fluconazole leads to a mean C Max) in fasted normal volunteers occur between 1 and 2 hours with a terminal plasma elimination half-life of approximately 30 hours (range: 20 to 50 hours) after oral administration. Bioequivalence was established between the 100 mg tablet and both suspension strengths when administered as a single 200 mg dose. In normal volunteers, the bioavailability of orally administered fluconazole is over 90% compared with intravenous administration. The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral routes.
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