Donovan M D, Flynn G L, Amidon G L
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Pharm Res. 1990 Aug;7(8):863-8. doi: 10.1023/a:1015921101465.
Polyethylene glycols (PEGs) 600, 1000, and 2000 were used to study the molecular weight permeability dependence in the rat nasal and gastrointestinal mucosa. Absorption of the PEGs was measured by following their urinary excretion over a 6-hr collection period. HPLC methods were used to separate and quantitate the individual oligomeric species present in the PEG samples. The permeabilities of both the gastrointestinal and the nasal mucosae exhibited similar molecular weight dependencies. The steepest absorption dependence for both mucosae occurs with the oligomers of PEG 600, where the extent of absorption decreases from approximately 60% to near 30% over a molecular weight range of less than 300 daltons. Differences in the absorption characteristics between the two sites appear in the molecular weight range spanned by PEG 1000. For these oligomers, the mean absorption from the nasal cavity is approximately 14%, while that from the gastrointestinal tract is only 9%. For PEG 2000, mean absorption decreases to 4% following intranasal application and below 2% following gastrointestinal administration. Within the PEG 1000 and 2000 samples, however, very little molecular weight dependency is seen among the oligomers. In the range studied, a distinct molecular weight cutoff was not apparent at either site.
聚乙二醇(PEG)600、1000和2000被用于研究大鼠鼻黏膜和胃肠道黏膜中分子量与渗透性的关系。通过在6小时收集期内跟踪其尿液排泄来测量PEG的吸收情况。采用高效液相色谱法分离和定量PEG样品中存在的各个低聚体种类。胃肠道黏膜和鼻黏膜的渗透性均表现出相似的分子量依赖性。两种黏膜的吸收依赖性在PEG 600的低聚物中最为明显,在小于300道尔顿的分子量范围内,吸收程度从约60%降至近30%。两个部位吸收特性的差异出现在PEG 1000所涵盖的分子量范围内。对于这些低聚物,鼻腔的平均吸收率约为14%,而胃肠道仅为9%。对于PEG 2000,鼻内给药后平均吸收率降至4%,胃肠道给药后低于2%。然而,在PEG 1000和2000样品中,低聚物之间几乎没有观察到分子量依赖性。在所研究的范围内,两个部位均未出现明显的分子量截断现象。