Ma T Y, Hollander D, Krugliak P, Katz K
Department of Medicine, University of California, Irvine.
Gastroenterology. 1990 Jan;98(1):39-46. doi: 10.1016/0016-5085(90)91288-h.
There is a widely held misconception that low-molecular-weight polyethylene glycols are "highly lipophilic" permeability probes and therefore are transported across lipid cell membranes. The relative lipophilicity of polyethylene glycols 400 and 600 were examined by determining their partition coefficients (Kd) in water and organic solvents of increasing relative polarity. The Kd of polyethylene glycol 414 between hexane and water was 0.000015, indicating that there are only 1.5 parts of polyethylene glycol 414 in hexane for 100,000 parts of polyethylene glycol 414 in water. When the Kd was determined in organic solvents with increasing relative polarity or "water character", there was a linear increase in Kd. The relative urinary recovery of individual molecular weight fractions of polyethylene glycol 400 in normal volunteers was analyzed. After oral ingestion, there was a progressive decrease in relative urinary recovery of increasing molecular weight fractions of polyethylene glycol 400 suggesting that increase in the molecular size limited polyethylene glycol intestinal permeability. There was excellent correlation between the relative urinary recovery and the hydrophilicity of the intravenously administered polyethylene glycol 400 fractions. It is concluded that polyethylene glycols 400 and 600 are strongly hydrophilic. Since partitioning of polyethylene glycol into lipid phase is negligible in lipid/water mixtures, they are unlikely to be transported via lipid pathways. The intestinal permeability of polyethylene glycols are governed by their molecular size, and once in circulation their urinary excretion appears to be governed in part by their plasma or water solubility.
有一种广泛存在的误解，认为低分子量聚乙二醇是“高度亲脂性”的通透性探针，因此能穿过脂质细胞膜。通过测定聚乙二醇400和600在相对极性递增的水和有机溶剂中的分配系数（Kd），来检测它们的相对亲脂性。聚乙二醇414在己烷和水之间的Kd为0.000015，这表明在水中的100,000份聚乙二醇414中，在己烷中只有1.5份聚乙二醇414。当在相对极性或“水特性”递增的有机溶剂中测定Kd时，Kd呈线性增加。分析了正常志愿者中聚乙二醇400各个分子量级分的相对尿回收率。口服后，聚乙二醇400分子量级分增加，其相对尿回收率逐渐降低，这表明分子大小的增加限制了聚乙二醇的肠道通透性。静脉注射的聚乙二醇400级分的相对尿回收率与亲水性之间存在极好的相关性。得出的结论是，聚乙二醇400和600具有很强的亲水性。由于在脂质/水混合物中聚乙二醇分配到脂质相的量可忽略不计，它们不太可能通过脂质途径转运。聚乙二醇的肠道通透性由其分子大小决定，一旦进入循环，其尿排泄似乎部分由其血浆或水溶性决定。
