PARTITION-COEFFICIENTS OF LOW-MOLECULAR-WEIGHT VOLATILE CHEMICALS IN VARIOUS LIQUIDS AND TISSUES
PARTITION-COEFFICIENTS OF LOW-MOLECULAR-WEIGHT VOLATILE CHEMICALS IN VARIOUS LIQUIDS AND TISSUES
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DOI：
10.1016/0041-008x(89)90137-3
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发表时间：
1989-03-15
影响因子：
3.8
通讯作者：
ANDERSEN, ME
中科院分区：
文献类型：
--
作者：
GARGAS, ML;BURGESS, RJ;ANDERSEN, ME
开发用于评估挥发性化学品在哺乳动物中的吸收、分布、禁忌和消除的生理学药代动力学模型需要分配系数。本文提出了一种测定低分子量挥发性化学品液气分配系数的气相小瓶平衡技术。这种技术是从两个先前描述的介质：空气方法，完全依赖于气相中的化学浓度的测量，并与早期的工作相比，扩大了化学品和组织检查的范围。用0.9%盐水、橄榄油和大鼠血液、肝脏、肌肉和脂肪组织测定55种化合物的分配系数。测定了36种化合物的人体血液：空气系数，还测定了小鼠和仓鼠中一种化合物的几种血液：空气值。描述了一种基于油：空气和盐水：空气系数，使用回归分析来预测未经测试的化合物的组织溶解度的方法。类似的方法用于根据油：空气值对脂肪：空气系数进行建模，并根据大鼠血液：空气系数对人类血液：空气系数进行建模。
Partition coefficients are required for developing physiologically based pharmacokinetic models used to assess the uptake, distribution, tabolism and elimination of volatile chemicals in mammals. A gas-phase vial equilibration technique is presented for determining the liquid:air partition coefficients for low-molecular-weight volatile chemicals. This technique was developed from two previously described medium:air methods, relied solely on measurement of chemical concentration in the gas phase, and, compared to earlier work, extends the range of chemicals and tissues examined. Partition coefficients were determined with 0.9% saline, olive oil, and blood, liver, muscle, and fat tissues from rats for 55 compounds. Human blood:air coefficients were determined for 36 compounds and several blood:air values were also determined in the mouse and for one compound in the hamster. An approach is described for predicting the tissue solubilities of untested compounds based on oil:air and saline:air coefficients using regression analyses. A similar approach is used to model fat:air coefficients in terms of oil:air values and to model human blood:air coefficients in terms of rat blood:air coefficients.