PHARMACOKINETICS OF FLUCONAZOLE IN SALIVA AND PLASMA AFTER ADMINISTRATION OF AN ORAL SUSPENSION AND CAPSULES

The concentrations of fluconazole were determined at steady state in t he saliva and plasma of 10 healthy volunteers after ingestion of fluco nazole as capsules and after flushing the mouth for 2 min with the sam e dose formulated as an oral suspension and swallowing of the drug. Sa liva and plasma samples were analyzed by a validated high-performance liquid chromatographic assay. Flushing and swallowing of the oral susp ension resulted in a significantly (P = 0.005) higher mean area under the concentration-versus-time curve (AUC) from 0 to 24 h in saliva (89 .13 +/- 23.42 mg . h/liter) than that obtained after ingestion of the same dose as capsules (69.27 +/- 12.89 mg . h/liter). The calculated m ean maximum concentration in saliva just after swallowing of the suspe nsion was 97.99 +/- 6.12 mg/liter. The peak fluconazole concentration in saliva after the ingestion of the capsules was 3.55 +/- 0.40 mg/lit er. The fluconazole oral suspension and capsules resulted in comparabl e concentrations and AUCs in plasma. Thus, because of a higher local l evel of drug exposure in terms of both higher peak concentrations in s aliva and a higher salivary AUC, the fluconazole oral suspension has t heoretical advantages over the capsule formulation in the treatment of oropharyngeal candidiases.