In vivo assessment and prediction of topical bioavailability of iodiconazole, a new triazole antifungal agent

Objective\r\nTo assess the in vivo cutaneous bioavailability of iodiconazole in a topical formulation.\r\n\r\n\r\nMethods\r\nIodiconazole 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.\r\n\r\n\r\nResults\r\nThe 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.\r\n\r\n\r\nConclusions\r\nAfter 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 phase Ⅱ study for iodiconazole.\r\n\r\n\r\nKey words: \r\nDermatopharmacokinetics; Bioavailability; Tape stripping; Stratum corneum; Skin absorption; Iodiconazole