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Prednisolone (PN) and an esterified derivative (PND) were evaluated in pharmacological and pharmacokinetic studies. The pharmacological study was performed using a rat croton-oil induced ear edema model. The results for the topical effect in skin and the systemic effect through multiple topical applications showed that PN and PND were equally potent in suppressing edema, and that PN caused a reduction in thymus weight, whereas PND had little effect. The concentration of these steroids in hairless mouse skin was estimated from an in vitro percutaneous absorption 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 microg/cm2), even after 7 d. However, the estimated concentration of PND in the viable skin appears to be in excess of the threshold for effective topical effect during the pharmacological evaluation. In contrast, in the case of PN, the estimated PN concentration increased gradually after application and reached a level of 10.22 microg/cm2 at day 7, suggesting that this increase in PN concentration in the viable skin could result in a systemic effect. The difference 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 reflected from the results of the pharmacokinetics of PN and PND in the skin.

Evaluation of the Topical Delivery of a Prednisolone Derivative Based upon Percutaneous Penetration Kinetic Analysis.