Iodiconazole is a novel antifungal agent that was developed in its racemic form. In order to investigate the ef- fects of the chiral center on the antifungal activity, R- and S-isomers of iodiconazole were prepared on...Iodiconazole is a novel antifungal agent that was developed in its racemic form. In order to investigate the ef- fects of the chiral center on the antifungal activity, R- and S-isomers of iodiconazole were prepared on the basis of the asymmetric Sharpless epoxidation. （S）-Iodiconazole was proved to have better antifungal activity than the （R）- isomer. The binding modes of the two isomers with lanosterol 14~z-demethylase were clarified by molecular dock- ing.展开更多
Objective To assess the in vivo cutaneous bioavailability of iodiconazole in a topical formulation. Methods Iodiconazole cream was topically administrated to the ventral forearms of 10 healthy volunteers for 1 hour, a...Objective To assess the in vivo cutaneous bioavailability of iodiconazole in a topical formulation. Methods Iodiconazole cream was topically administrated to the ventral forearms of 10 healthy volunteers for 1 hour, and the excess formulation was removed. The stratum corneum (SC) at the application sites was tape-stripped immediately or at different time points, quantified gravimetrically, and extracted for analysis. Together with concomitant transepidermal water loss (TEWL) measurement, SC drug concentration-depth profiles were reproducibly determined and fitted mathematically to obtain the SC-vehicle partition coefficient (K) and a first-order rate constant (D/L2) related to iodiconazole diffusivity. The main pharmacokinetic parameters were calculated by Drug and Statistics software. With these parameters, the uptake of iodiconazole of time into SC was assessed. The variation of iodiconazole concentrations in stratum corneum post-removal of the formulation was also investigated. Results The mean values of K and D/L2 of 10 healthy volunteers were (0.13 ± 0.07) and (0.15 ± 0.08)/hour, respectively. The classic lag-time for diffusion (Tlag) across the SC varied from 0.52 hours to 2.28 hours. The mean value of time to reach steady-state transport (Tss) was (3.74 ± 1.69) hours. The mean values of the elimination half-life (t1/2) and the elimination rate constant (Kel) of 10 healthy volunteers were (8.47 ± 5.36) hours and (0.11 ± 0.05)/hour, respectively. Conclusions After topical application, iodiconaole penetrated into the SC rapidly and maintained a high concentration at the target site. The results of this study can provide reliable evidences for the clinical medication and the design of following phaseⅡstudy for iodiconazole.展开更多
基金the National Natural Science Foundation of China，Shanghai Municipal Health Bureau
文摘Iodiconazole is a novel antifungal agent that was developed in its racemic form. In order to investigate the ef- fects of the chiral center on the antifungal activity, R- and S-isomers of iodiconazole were prepared on the basis of the asymmetric Sharpless epoxidation. （S）-Iodiconazole was proved to have better antifungal activity than the （R）- isomer. The binding modes of the two isomers with lanosterol 14~z-demethylase were clarified by molecular dock- ing.
文摘Objective To assess the in vivo cutaneous bioavailability of iodiconazole in a topical formulation. Methods Iodiconazole cream was topically administrated to the ventral forearms of 10 healthy volunteers for 1 hour, and the excess formulation was removed. The stratum corneum (SC) at the application sites was tape-stripped immediately or at different time points, quantified gravimetrically, and extracted for analysis. Together with concomitant transepidermal water loss (TEWL) measurement, SC drug concentration-depth profiles were reproducibly determined and fitted mathematically to obtain the SC-vehicle partition coefficient (K) and a first-order rate constant (D/L2) related to iodiconazole diffusivity. The main pharmacokinetic parameters were calculated by Drug and Statistics software. With these parameters, the uptake of iodiconazole of time into SC was assessed. The variation of iodiconazole concentrations in stratum corneum post-removal of the formulation was also investigated. Results The mean values of K and D/L2 of 10 healthy volunteers were (0.13 ± 0.07) and (0.15 ± 0.08)/hour, respectively. The classic lag-time for diffusion (Tlag) across the SC varied from 0.52 hours to 2.28 hours. The mean value of time to reach steady-state transport (Tss) was (3.74 ± 1.69) hours. The mean values of the elimination half-life (t1/2) and the elimination rate constant (Kel) of 10 healthy volunteers were (8.47 ± 5.36) hours and (0.11 ± 0.05)/hour, respectively. Conclusions After topical application, iodiconaole penetrated into the SC rapidly and maintained a high concentration at the target site. The results of this study can provide reliable evidences for the clinical medication and the design of following phaseⅡstudy for iodiconazole.
