title: Pharmacokinetics of fluconazole in saliva and plasma after administration of an oral suspension and capsules.
abstract: The concentrations of fluconazole were determined at steady state in the saliva and plasma of 10 healthy volunteers after ingestion of fluconazole as capsules and after flushing the mouth for 2 min with the same dose formulated as an oral suspension and swallowing of the drug. Saliva and plasma samples were analyzed by a validated high-performance liquid chromatographic assay. Flushing and swallowing of the oral suspension 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 mean maximum concentration in saliva just after swallowing of the suspension 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/liter. The fluconazole oral suspension and capsules resulted in comparable concentrations and AUCs in plasma. Thus, because of a higher local level of drug exposure in terms of both higher peak concentrations in saliva and a higher salivary AUC, the fluconazole oral suspension has theoretical advantages over the capsule formulation in the treatment of oropharyngeal candidiases.
authors.affiliation: Department of Pharmacy, Slotervaart Hospital, Amsterdam, The Netherlands.
authors.forename: C H
authors.initials: CH
authors.lastname: Koks
authors.forename: P L
authors.initials: PL
authors.lastname: Meenhorst
authors.forename: M J
authors.initials: MJ
authors.lastname: Hillebrand
authors.forename: A
authors.initials: A
authors.lastname: Bult
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002214:Capsules; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D012463:Saliva / Q000378:metabolism*; D013535:Suspensions
chemical_list: D000935:Antifungal Agents; D002214:Capsules; D013535:Suspensions; D015725:Fluconazole