Hashiguchi T, Takada A, Ikesue A, Ohta J, Yamaguchi T, Yasutake T, Otagiri M
Tsukuba Laboratories, Hisamitsu Pharmaceutical Co., Inc., Ibaraki, Japan.
Biol Pharm Bull. 1998 Aug;21(8):882-5. doi: 10.1248/bpb.21.882.
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.
在药理学和药代动力学研究中对泼尼松龙（PN）及其酯化衍生物（PND）进行了评估。药理学研究使用大鼠巴豆油诱导的耳水肿模型进行。皮肤局部效应及多次局部应用后的全身效应结果表明，PN和PND在抑制水肿方面同样有效，且PN导致胸腺重量减轻，而PND几乎没有影响。通过使用计算机模拟程序MULTI(FILT)的体外经皮吸收研究估算了这些类固醇在无毛小鼠皮肤中的浓度。发现PND吸收较差。事实上，即使在7天后，活性皮肤中PND的浓度仍很低（0.79微克/平方厘米）。然而，在药理学评估期间，活性皮肤中PND的估算浓度似乎超过了有效局部效应的阈值。相比之下，对于PN，应用后估算的PN浓度逐渐增加，在第7天达到10.22微克/平方厘米的水平，这表明活性皮肤中PN浓度的这种增加可能导致全身效应。在整个时间过程中，PN和PND在皮肤中的浓度差异可能是由于PND在活性皮肤中代谢为PN所致。因此，药理学研究中的差异从PN和PND在皮肤中的药代动力学结果中得以体现。
