Fluconazole: comparison of pharmacokinetics, therapy and in vitro susceptibility

Abstract

Fluconazole shows good penetration into the tissues and body fluids examined and a rapid equilibrium is achieved between the concentrations in the various compartments. The pharmacokinetics of fluconazole after intravenous or oral administration are proportional to the dose. This finding, together with the slow elimination of the triazole (t1/2 30 h), makes it easier to forecast the therapeutically effective dosage. Measurements of fluconazole concentration in blood can be used to predict levels in some tissues (lung, brain, gynaecological samples), body fluids (sputum, saliva, vaginal secretions) or exudates. Concentrations in cerebrospinal fluid and vitreous humour of the eye reach approximately 80% of the levels found in blood. A very high proportion of fluconazole is excreted unchanged in the urine, where concentrations of the drug are 10-20-fold higher than in blood. Whilst this pharmacokinetic profile is valuable in the treatment of fungal infections of the urinary tract, it also means that the dosage may need to be decreased in patients with renal impairment. The susceptibility of fungi to fluconazole in vitro and in vivo correlates well with the concentrations of the drug measured in various compartments of the body.

Tissue Penetration of Antifungal Agents

“…The pericardial fluid/plasma concentration ratios of fluconazole in 20 patients ranged from 0.9 to 1.0 (136). Data from a single patient with disseminated aspergillosis also suggest that voriconazole diffuses into the pericardial fluid, at a concentration comparable to the plasma concentration (153).…”

“…In 20 patients receiving a single 200-mg dose of fluconazole, the lung tissue/plasma concentration ratio range was 1.1 to 1.6 (136). Similarly, the fluconazole ELF/plasma concentration ratio in cats was 1.2 (137).…”

“…doses, fluconazole is also detectable in the nucleus pulposus of the rabbit spine, but with a very wide concentration range (0 to 63.5 g/g) that is apparently unrelated to concentrations in plasma (204). In three patients, fluconazole synovial fluid concentrations were 0.88 to 1.0 times those in plasma (136,205,206). Similarly, the mean synovial fluid/plasma concentration ratio of fluconazole after 10 days of dosing to horses was 0.5 (207).…”

Acute adrenal failure associated with fluconazole after administration of high‐dose cyclophosphamide

“…In a prospective, randomized, placebo-controlled trial, fluconazole at a dosage of 400 mg/day was shown to significantly reduce fungal colonization, superficial and hematogenous candidiasis, and mortality [2]. Because fluconazole is well absorbed from the gastrointestinal tract, and there is little associated toxicity [3], this anti-fungal agent is now widely used in chemoprophylaxis in cases involving a risk of opportunistic mycoses.…”

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

“…Penetration into other body tissues such as joint spaces, saliva, vaginal secretions, and vitreous humor of the eye also approximate levels found in the serum. Fluconazole is eliminated primarily through the kidneys and excreted largely unchanged resulting in urine concentrations 10-20 times higher than those found in blood [53,54].…”