Fujii M, Yamanouchi S, Hori N, Iwanaga N, Kawaguchi N, Matsumoto M
Showa College of Pharmaceutical Sciences, Machida, Japan.
Biol Pharm Bull. 1997 Mar;20(3):249-54. doi: 10.1248/bpb.20.249.
Skin permeation rates of five non-steroidal anti-inflammatory drugs, three of them lipophilic (ibuprofen, indomethacin and ketoprofen) and two hydrophilic (sodium diclofenac and antipyrine), through Yucatan hairless micropig (YMP) full-thickness skin were determined in vitro using Franz-type diffusion cells, and the usefulness of YMP skin as an animal model skin was investigated. Five-month-old YMP skin showed small variation with respect to drug permeation rates, if the region of skin site was the same. But skin from 6-month-old YMPs showed faster and varied permeation rates due to skin defects. In the case of hydrophilic drugs, no effects on permeation due to the region from which the skin was obtained were observed, although higher permeation rates were observed through the flank than through dorsal skin in the case of ibuprofen and ketoprofen. For YMP skin, the permeation coefficients of drugs were lower than those for hairless rat skin, especially for hydrophilic drugs. Compared with reported human data on permeation coefficients, the permeation coefficients of drugs through YMP skin were 1/2-1/8 of those through human skin, regardless of whether the drugs were hydrophilic or lipophilic. YMP skin could be used as an in vitro animal skin model because of the reproducibility of the permeation rate of drugs through this skin and its similarity to human skin.
使用弗兰兹型扩散池体外测定了五种非甾体抗炎药通过尤卡坦无毛微型猪(YMP)全层皮肤的透皮速率,其中三种为亲脂性药物(布洛芬、吲哚美辛和酮洛芬),两种为亲水性药物(双氯芬酸钠和安替比林),并研究了YMP皮肤作为动物模型皮肤的实用性。如果皮肤部位相同,五个月龄YMP的皮肤在药物透皮速率方面变化较小。但六个月龄YMP的皮肤由于皮肤缺陷,透皮速率更快且存在差异。对于亲水性药物,未观察到皮肤取材部位对其渗透有影响,不过在布洛芬和酮洛芬的情况下,通过胁腹皮肤的渗透速率高于背部皮肤。对于YMP皮肤,药物的渗透系数低于无毛大鼠皮肤,尤其是亲水性药物。与已报道的人体渗透系数数据相比,无论药物是亲水性还是亲脂性,通过YMP皮肤的药物渗透系数是通过人体皮肤的1/2至1/8。由于药物通过这种皮肤的渗透速率具有可重复性且与人体皮肤相似,YMP皮肤可作为体外动物皮肤模型。