title: Accumulation of fluconazole in sebum.
abstract: Concentrations of fluconazole in sebum and plasma were determined in 2 parallel groups, each consisting of 8 healthy subjects. Group 1 received a 150 mg fluconazole capsule once weekly over a period of 4 weeks, Group 2 was administered 2 capsules/week, corresponding to 300 mg fluconazole/week for 4 weeks. Sampling was performed immediately before and 5 hours after dosing, and at intervals up to 2 weeks after the last dose. Fluconazole concentrations were determined by a specific and highly sensitive gas chromatographic method. Both treatments were well tolerated. Maximum fluconazole concentrations (mean +/- SD) in plasma were 3.5 +/- 1.0 microg/ml (Group 1) and 5.5 +/- 1.0 microg/ml (Group 2); maximum sebum concentrations were 11.0 +/- 8.4 microg/g (Group 1) and 48.4 +/- 37.0 microg/g (Group 2). Significant accumulation of fluconazole in sebum relative to plasma was observed. Sebum/plasma ratios ranged from 1.6 to 6.5 (Group 1) and from 4.3 to 27.9 (Group 2), with median ratios of 2.4 and 9.1, respectively. The overall accumulation factor was 7. The findings may be of particular relevance for the treatment of dermal mycoses involving the sebaceous glands, especially those associated with hair, such as tinea capitis.
authors.affiliation: Pfizer Research and Development, Illertissen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Zimmermann
authors.forename: H
authors.initials: H
authors.lastname: Laufen
authors.forename: R A
authors.initials: RA
authors.lastname: Yeates
authors.forename: F
authors.initials: F
authors.lastname: Scharpf
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002849:Chromatography, Gas; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D012016:Reference Values; D012629:Sebum / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole