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Accumulation of fluconazole in scalp hair
R Yeates1, H Laufen, T Zimmermann
1Department of Pharmacology, Pfizer Mack Development Centre, Illertissen, Germany.
Abstract:
The accumulation in scalp hair of the antimycotic triazole, fluconazole, was studied during and after administration. Fluconazole 50 mg was administered to 12 healthy subjects as a single capsule each day for 28 days. The concentration of fluconazole 5 hours after administration was measured in different 1-cm sections of scalp hair at intervals during treatment and for 6 months after the end of treatment. In each section of scalp hair the concentration of fluconazole increased during treatment and was consistently higher than values found in plasma. For example, the mean concentration in the first hair section on day 28, 19.8 micrograms/g, corresponded to a mean penetration ratio relative to plasma of 9.42. During administration, the maximal concentration of fluconazole was found in the first hair section. After cessation of administration, the measured concentrations of fluconazole decreased and greater concentrations were found in the distal hair sections, presumably as a result of hair growth. Fluconazole was detectable, however, in the hair of 9 of the 12 subjects even 6 months after treatment. The mean concentration of fluconazole in hair bulbs on day 28 was 12.1 micrograms/g (n = 6), corresponding to a mean penetration ratio of 5.99. In a second study, fluconazole was administered as a single oral 150-mg capsule per week for 4 weeks to a group of 8 healthy subjects. The mean fluconazole concentration in whole scalp hair 5 hours after the last dose was 3.2 micrograms/g.
Insights
Fluconazole accumulates in scalp hair, reaching concentrations higher than plasma during treatment. This antifungal drug remains detectable in hair for up to six months after therapy cessation.
Area of Science:
- Pharmacokinetics
- Dermatology
- Mycology
Background:
- Fluconazole is a widely used triazole antifungal agent.
- Understanding drug accumulation in hair is crucial for assessing treatment efficacy and duration.
- Scalp hair offers a matrix for long-term drug concentration monitoring.
Purpose of the Study:
- To quantify fluconazole accumulation in human scalp hair during and after oral administration.
- To compare fluconazole concentrations in hair with plasma levels.
- To determine the persistence of fluconazole in hair post-treatment.
Main Methods:
- Healthy subjects received daily oral fluconazole (50 mg) for 28 days or weekly (150 mg) for 4 weeks.
- Fluconazole concentrations were measured in scalp hair sections and plasma at various time points.
- Hair samples were analyzed using chromatography techniques.
Main Results:
- Fluconazole concentrations in scalp hair increased during treatment and were consistently higher than plasma levels.
- Mean hair-to-plasma concentration ratios reached up to 9.42.
- Fluconazole was detectable in hair up to 6 months after treatment cessation in most subjects.
Conclusions:
- Scalp hair effectively accumulates fluconazole, serving as a long-term reservoir.
- Hair drug concentrations correlate with systemic exposure and treatment duration.
- These findings support the use of hair analysis for monitoring fluconazole therapy.