Hilton J, Woollen B H, Scott R C, Auton T R, Trebilcock K L, Wilks M F
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, England.
Pharm Res. 1994 Oct;11(10):1396-400. doi: 10.1023/a:1018931503784.
We studied the effects of three vehicles (propylene glycol, octanol and ethyl decanoate) with differing polarity on the in vitro percutaneous absorption of three chemicals (fluazifop-butyl, dimethyl phthalate and fomesafen sodium salt) with a range of physico-chemical properties. Absorption rate measurements were made from high vehicle volume (200 microliters/cm2) and low vehicle volume (< 10 microliters/cm2) applications. For the lipophilic fluazifop-butyl absorption rate was highest from the more polar vehicle propylene glycol, but this effect was only significant under high-volume conditions. There was a variable vehicle effect on absorption of the intermediate chemical dimethyl phthalate. The largest vehicle effect was seen for the more hydrophilic fomesafen sodium salt where absorption was fastest from the least polar vehicle ethyl decanoate. These results support the hypothesis that the absorption process can in part be predicted from a knowledge of solute solubility. Vehicle effects were greater from high volume applications than from those more comparable to occupational exposure conditions.
我们研究了三种具有不同极性的赋形剂(丙二醇、辛醇和癸酸乙酯)对三种具有一系列物理化学性质的化学品(精稳杀得、邻苯二甲酸二甲酯和乙羧氟草醚钠盐)体外经皮吸收的影响。在高赋形剂体积(200微升/平方厘米)和低赋形剂体积(<10微升/平方厘米)应用条件下进行了吸收率测量。对于亲脂性的精稳杀得,从极性更强的赋形剂丙二醇中的吸收率最高,但这种效应仅在高体积条件下显著。对于中等亲脂性的邻苯二甲酸二甲酯的吸收,赋形剂有可变效应。对于亲水性更强的乙羧氟草醚钠盐,赋形剂效应最大,从极性最小的赋形剂癸酸乙酯中的吸收最快。这些结果支持了这样一种假设,即吸收过程部分可以根据溶质溶解度的知识来预测。高体积应用的赋形剂效应比与职业暴露条件更相似的应用的赋形剂效应更大。