The Cmax and AUC data from a food-effect study involving administration of DIFLUCAN (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. Therefore, DIFLUCAN may be taken without regard to meals. (see DOSAGE AND ADMINISTRATION.)

Administration of a single oral 150 mg tablet of DIFLUCAN (fluconazole) to ten lactating women resulted in a mean Cmax of 2.61 µg/mL (range: 1.57 to 3.65 µg/mL).

Steady-state concentrations are reached within 5–10 days following oral doses of 50–400 mg given once daily. 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. The apparent volume of distribution of fluconazole approximates that of total body water. Plasma protein binding is low (11–12%). Following either single- or multiple oral doses for up to 14 days, fluconazole penetrates into all body fluids studied (see table below). In normal volunteers, saliva concentrations of fluconazole were equal to or slightly greater than plasma concentrations regardless of dose, route, or duration of dosing. In patients with bronchiectasis, sputum concentrations of fluconazole following a single 150 mg oral dose were equal to plasma concentrations at both 4 and 24 hours post dose. In patients with fungal meningitis, fluconazole concentrations in the CSF are approximately 80% of the corresponding plasma concentrations.

A single oral 150 mg dose of fluconazole administered to 27 patients penetrated into vaginal tissue, resulting in tissue:plasma ratios ranging from 0.94 to 1.14 over the first 48 hours following dosing.

A single oral 150 mg dose of fluconazole administered to 14 patients penetrated into vaginal fluid, resulting in fluid:plasma ratios ranging from 0.36 to 0.71 over the first 72 hours following dosing.

Tissue or Fluid Ratio of Fluconazole Tissue (Fluid)/Plasma Concentration*
*
Relative to concurrent concentrations in plasma in subjects with normal renal function.
†
Independent of degree of meningeal inflammation. 
Cerebrospinal fluid† 0.5–0.9
Saliva 1
Sputum 1
Blister fluid 1
Urine 10
Normal skin 10
Nails 1
Blister skin 2
Vaginal tissue 1
Vaginal fluid 0.4–0.7

In normal volunteers, fluconazole is cleared primarily by renal excretion, with approximately 80% of the administered dose appearing in the urine as unchanged drug. About 11% of the dose is excreted in the urine as metabolites.

The pharmacokinetics of fluconazole are markedly affected by reduction in renal function. There is an inverse relationship between the elimination half-life and creatinine clearance. The dose of DIFLUCAN may need to be reduced in patients with impaired renal function. (See DOSAGE AND ADMINISTRATION.) A 3-hour hemodialysis session decreases plasma concentrations by approximately 50%.

In normal volunteers, DIFLUCAN administration (doses ranging from 200 mg to 400 mg once daily for up to 14 days) was associated with small and inconsistent effects on testosterone concentrations, endogenous corticosteroid concentrations, and the ACTH-stimulated cortisol response.

Pharmacokinetics in Children
In children, the following pharmacokinetic data {Mean (%cv)} have been reported:

Age
Studied Dose
(mg/kg) Clearance
(mL/