This study investigated the use of HWY hairless rats to predict human plasma concentrations of drugs following dermal application.Utilizing a deconvolution method, pharmacokinetic parameters (e.g. in vivo absorption rates) were determined for six transdermal drugs in hairless rats. Obtained data were used to simulate the human plasma concentration-time profiles of transdermal drugs, which were then compared with clinical data in humans. Because hairless rats have lower hair follicle density than do humans, the impact of hair follicle density on skin permeability to hydrophilic compounds was also evaluated.Pharmacokinetic parameters showed low intra-individual variability in hairless rats. Simulated concentration profiles for compounds with logarithm of the octanol-water partition coefficient exceeding two were comparable to clinical data, but simulated concentration profiles for hydrophilic compounds (i.e. bisoprolol and nicotine) at maximum concentration differed from clinical data by more than two-fold. Finally, in vitro permeability to bisoprolol and nicotine was higher in human skin than in hairless rat skin, but hair follicle plugging reduced human skin permeability.In vivo skin absorption data from HWY hairless rats help to predict human concentration profiles for lipophilic compounds. However, the data underestimate human absorption of hydrophilic compounds.

中文翻译：

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无毛大鼠作为预测人类透皮药代动力学模型的实用程序。

这项研究调查了使用HWY无毛大鼠预测皮肤应用后人体血浆药物的浓度。利用去卷积方法，确定了无毛大鼠中六种经皮药物的药代动力学参数（例如体内吸收率）。将获得的数据用于模拟透皮药物的人血浆浓度-时间曲线，然后将其与人的临床数据进行比较。由于无毛大鼠的毛囊密度低于人类，因此还评估了毛囊密度对皮肤对亲水性化合物渗透性的影响。药代动力学参数显示，无毛大鼠的个体内变异性较低。辛醇-水分配系数对数超过2的化合物的模拟浓度曲线与临床数据相当，但是最大浓度下亲水化合物（即比索洛尔和尼古丁）的模拟浓度曲线与临床数据相差超过两倍。最后，比索洛尔和尼古丁在人皮肤中的体外渗透性高于无毛大鼠皮肤，但毛囊堵塞降低了人皮肤的渗透性.HWY无毛大鼠的体内皮肤吸收数据有助于预测人亲脂性化合物的浓度曲线。但是，这些数据低估了人体对亲水性化合物的吸收。HWY无毛大鼠的体内皮肤吸收数据有助于预测人类亲脂性化合物的浓度曲线。但是，这些数据低估了人体对亲水性化合物的吸收。HWY无毛大鼠的体内皮肤吸收数据有助于预测人类亲脂性化合物的浓度曲线。但是，这些数据低估了人体对亲水性化合物的吸收。