EVALUATION OF THE TOPICAL DELIVERY OF A PREDNISOLONE DERIVATIVE BASEDUPON PERCUTANEOUS PENETRATION KINETIC-ANALYSIS

Prednisolone (PN) and an esterified derivative (PND) were evaluated in pharmacological and pharmacokinetic studies. The pharmacological stud y was performed using a rat croton-oil induced ear edema model. The re sults for the topical effect in skin and the systemic effect through m ultiple topical applications showed that PN and PND were equally poten t in suppressing edema, and that PN caused a reduction in thymus weigh t, whereas PND had little effect. The concentration of these steroids in hairless mouse skin was estimated from an ill vitro percutaneous ab sorption study using the computer simulation program MULTI(FILT). PND was found to be poorly absorbed. In fact, the PND concentration in the viable skin remained low (0.79 g/cm(2)), even after 7 d. However, the estimated concentration of PND in the viable skin appears to be in ex cess of the threshold for effective topical effect during the pharmaco logical evaluation, In contrast, in the case of PN, the estimated PN c oncentration increased gradually after application and reached a level of 10.22 mu g/cm(2) at day 7, suggesting that this increase in PN con centration in the viable skin could result in a systemic effect. The d ifference between PN and PND concentration in the skin during the time course could be due to the metabolism of PND to PN in the viable skin . Consequently, the difference between the pharmacological study is re flected from the results of the pharmacokinetics of PN and PND in the skin.