Abraham Michael H, Ibrahim Adam, Acree William E
Department of Chemistry, University College London, UK.
Chem Res Toxicol. 2006 Jun;19(6):801-8. doi: 10.1021/tx050337k.
Distribution coefficients, K(mus), from the gas phase to the muscle have been collected for volatile organic compounds (VOCs). For 114 VOCs, a linear free energy relationship (LFER) yields an equation for log K(mus) with R(2) = 0.944 and SD = 0.267; construction of a training and test set shows that the LFER can predict further values to around 0.30 log units. The combination of the log K(mus) values with values for air to blood yields distribution coefficients from blood to muscle, log P(mus), for 110 VOCs; the corresponding LFER has R(2) = 0.537 and SD = 0.207 and a predictive capability of 0.22 log units. We also collected data on the distribution of drugs from blood or plasma to muscle and showed that the two sets of data can be combined. A LFER for blood/plasma to muscle for 59 drugs has R(2) = 0.745 and SD = 0.253 and a predictive capability of 0.25 log units. Finally, we show that the in vitro data on VOCs and the in vivo data on drugs can be combined; a LFER on the total data for 163 compounds has R(2) = 0.595, SD = 0.220, and a predictive capability of about 0.25 log units.
已收集了挥发性有机化合物（VOCs）从气相到肌肉的分配系数K(mus)。对于114种VOCs，线性自由能关系（LFER）得出了一个log K(mus)的方程，R(2)=0.944，标准差（SD）=0.267；训练集和测试集的构建表明，LFER可以将进一步的值预测到约0.30对数单位。将log K(mus)值与空气到血液的值相结合，得出了110种VOCs从血液到肌肉的分配系数log P(mus)；相应的LFER的R(2)=0.537，标准差（SD）=0.207，预测能力为0.22对数单位。我们还收集了药物从血液或血浆到肌肉的分布数据，并表明这两组数据可以合并。59种药物从血液/血浆到肌肉的LFER的R(2)=0.745，标准差（SD）=0.253，预测能力为0.25对数单位。最后，我们表明可以将VOCs的体外数据和药物的体内数据合并；163种化合物的总数据的LFER的R(2)=0.595，标准差（SD）=0.220，预测能力约为0.25对数单位。
