Pharmacokinetic optimization of the treatment of oral candidiasis with fluconazole: studies with a suspension.

An open crossover study was performed in 12 healthy subjects to investigate the pharmacokinetics in saliva and plasma of a 100 mg oral dose of fluconazole, administered as either a capsule or as a suspension, the latter being used to rinse the mouth and retained for 2 min before being swallowed. In terms of fluconazole plasma concentrations the capsule and the suspension were essentially bioequivalent. While the saliva concentrations of fluconazole after capsule administration reached their peak at 3.0 +/- 0.8 micrograms/ml 4 h after dosage, administration of the suspension resulted in a mean peak concentration of 551.1 +/- 425.6 micrograms/ml 5 min after ingestion. The saliva concentrations decreased gradually after ingestion of the suspension, but were higher for 4 h than the corresponding levels from the capsule. The area under the curve (AUC) from 0 to 96 h of fluconazole in saliva was 227.7 +/- 73.8 h micrograms/ml after the suspension, compared to 123.5 +/- 25.5 h micrograms/ml after the capsule, indicating that the total drug exposure to the oral mucosa by the salivary route was enhanced more than 80% with use of the suspension. Four h after administration of the suspension, saliva and plasma concentrations of fluconazole were in equilibrium, at a saliva: plasma ratio of around 1.2. Taken together, the present results suggest that the treatment of oral candidiasis with fluconazole may be optimized by use of an oral suspension, as this delivers pharmacologically active levels of the drug to the site of infection by both topical and systemic routes.