Frasch H Frederick, Landsittel Douglas P
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, MS L-3030, 1095 Willowdale Road, Morgantown, WV 26505, USA.
Eur J Pharm Sci. 2002 Jun;15(5):399-403. doi: 10.1016/s0928-0987(02)00053-2.
We investigated the sources of data used in recently published predictive models of skin permeability. It was found that skin permeability coefficients for 63 compounds are poorly documented. We hypothesized that these coefficients were calculated using the simple two variable, three parameter 'Potts and Guy' regression equation and hence were not derived from experimental measurements. We therefore examined the distribution of residuals of these reported coefficients compared with the Potts and Guy predictions. The residuals cannot be described by a normal distribution. A substantial (51%) number of residuals equaled 0.00. Further analysis demonstrated that 89% (56 out of 63) of the skin permeability coefficients can be explained as being calculated by the Potts and Guy equation using different documented octanol-water partition coefficients, and/or transcription errors. The results strongly suggest that these 63 skin permeability coefficients are calculated and not experimentally determined-a conclusion subsequently confirmed by one of the developers of the data set. Continued use of these data would lead to biased model selection, underestimation of experimental variability, and overestimation of model predictive ability.
我们调查了最近发表的皮肤渗透性预测模型中所使用的数据来源。结果发现，63种化合物的皮肤渗透系数记录不完善。我们推测这些系数是使用简单的双变量、三参数“Potts和Guy”回归方程计算得出的，因此并非来自实验测量。因此，我们将这些报告的系数的残差分布与Potts和Guy的预测结果进行了比较。残差无法用正态分布来描述。相当数量（51%）的残差等于0.00。进一步分析表明，89%（63个中的56个）的皮肤渗透系数可以解释为是通过Potts和Guy方程使用不同记录的正辛醇-水分配系数计算得出的，和/或转录错误。结果强烈表明，这63个皮肤渗透系数是计算得出的，而非实验测定——该数据集的一位开发者随后证实了这一结论。继续使用这些数据将导致有偏差的模型选择、对实验变异性的低估以及对模型预测能力的高估。
