In this study, the distribution of a new
triazole drug,
iodiconazole, in rat dermal interstitial fluid and blood was investigated by double-site microdialysis following
dermal administration. It was demonstrated that well-calibrated microdialysis sampling in rats could be used to assess the percutaneous penetration kinetics of
iodiconazole cream.
Iodiconazole penetrated rapidly and cleared slowly from the dermis. The ratio of area under the concentration-time curve in dermis (AUC(dermis)) to that in blood (AUC(blood)) was close to 20, which meant that the free
iodiconazole concentration had a higher distribution in the target tissue. Subsequently, the in vitro antifungal activities of
iodiconazole were evaluated and were compared with those of
fluconazole,
itraconazole,
ketoconazole,
miconazole and
terbinafine.
Iodiconazole exhibited broad spectrum and potent activity against 12 kinds of clinically pathogenic fungi. The
drug concentration percentage inhibition curves versus time of
iodiconazole against the tested fungi elucidated the two-dimensional relationship (concentration-effect) following
drug administration, indicating that the percentage inhibition (%) of
iodiconazole compared with the
drug-free control in dermal
dialysate were all >90% in the 900-min sampling time following
dermal administration. Moreover, integration of in vivo pharmacokinetic data with the in vitro minimum inhibitory concentration (MIC) provided
iodiconazole AUC/MIC ratios in rat dermis and blood of 347.7h and 18.8h, respectively, with an
iodiconazole cream (2%) dosage of 0.033 g/cm² (3 cm×5 cm). These findings show a reservoir effect in the skin following topical application.
Iodiconazole topical cream may be a future alternative for treatment of
dermatophytosis in humans.