Plasma concentrations of griseofulvin in healthy volunteers and out-patients treated for onychomycosis.

Therapeutic failure of griseofulvin therapy are fairly common, espcially when toe nail infections are treated. The reasons for the failures remain largely unknown. The aim of the present investigation was to study whether pharmacokinetic factors may be responsible. At first, single-dose and steady-state pharmacokinetics of griseofulvin were analysed in volunteers by means of a gas-chromatographic technique. It was found that there was no difference in plasma levels of the three brands of griseofulvin commercially available in Sweden, whereas there was a singificant difference of absorption between individuals. The plasma half-life varied considerably from day to day in the same individual. In the second part of the investigation griseofulvin plasma concentrations were determined in 27 patients treated with griseofulvin for onychomycosis and related to the therapeutic result. All patients but one were initially improved but the therapeutic effect faded in 15 patients after 5-20 months of treatment ("partially healed" patients). In 11 patients the nail infections were clinically healed after 6-24 months. However, no statistically significant difference of the plasma griseofilvin levels could be demonstrated between the healed and partially healed groups. Some possible reasons for the therapeutic failure are discussed.