Pharmacokinetics of griseofulvin in blood and skin suction blister fluid of rats.

The penetration of griseofulvin to its site of action was investigated in the rat using subepidermal blisters induced by suction as a model. Griseofulvin was administered iv at a dose of 20 mg/kg after which blood, suction blister fluid (SBF), and skin tissue were sampled over a 300-min time period. The blood level/time course can be described by a two-compartment model. During the terminal phase, concentrations of drug in blood, SBF, and cutis declined in parallel, with respective half-lives of 71.0, 70.4, and 74.6 min. In SBF, maximum concentrations (2.35 +/- 0.36 micrograms/ml) were obtained 60 min postinjection, drug levels increased until the concentrations of unbound griseofulvin in SBF and plasma were identical. Time to peak concentration in cutis was shorter (20 min; 13.9 +/- 0.5 micrograms/ml). As the dermatophytes are located in the horny layer, the determination of griseofulvin in SBF seems to be a more suitable assay for determining the griseofulvin level profile at its site of action. In addition, the level of unbound, and thus active, griseofulvin in SBF was severalfold lower than the concentration of total drug in excised skin tissue. Up to now, the latter value has been considered to indicate that the concentration of griseofulvin in the skin is comparable to the in vitro sensitivity of dermatophytes. The present results show that this seems to be no longer justified.