Accumulation of fluconazole in sebum

Concentrations of fluconazole in sebum and plasma were determined in 2 para llel 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 ad ministered 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 concentra tions were determined by a specific and highly sensitive gas chromatographi c method. Both treatments were well tolerated. Maximum fluconazole concentr ations (mean +/- SD) in plasma were 3.5 +/- 1.0 mug/ml (Group 1) and 5.5 +/ - 1.0 mug/ml (Group 2); maximum sebum concentrations were 11.0 +/- 8.4 mug/ g (Group 1) and 48.4 +/- 37.0 mug/g (Group 2). Significant accumulation of fluconazole in sebum relative to plasma was observed. Sebum/plasma ratios r anged 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 m ycoses involving the sebaceous glands, especially those associated with hai r, such as tinea capitis.