Sakaeda T, Takahashi K, Nishihara Y, Hirano K
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Biol Pharm Bull. 1994 Nov;17(11):1490-5. doi: 10.1248/bpb.17.1490.
The potential usefulness of oil in water (O/W) lipid emulsions as parenteral drug delivery system for lipophilic drugs was examined in tumor-bearing rats. A model lipophilic drug, sudan II (PCoct = 226000), was formulated in five lipid emulsions consisting of soybean oil and various surfactants. Compared with HCO-60 micellar and plasma solutions of sudan II, the blood concentration of sudan II was markedly elevated by administration as a lipid emulsion. However, the distribution of sudan II to the liver, lungs, spleen, and adipose tissue was not altered, and that to the brain, heart, kidneys, muscle, and tumor was slightly decreased. To understand these results, pharmacokinetic analysis was performed using a newly derived compartmental model, and moreover, the organ distribution clearance was analyzed. It was suggested that the oil particles deliver the incorporated drug selectively to the liver, lungs, and spleen, and the speed of delivery could be surpressed by using HCO-60. However, in the case of sudan II, its rapid release from the oil particles after i.v. injection prevented a drastic alteration in the distribution of sudan II. The simulation studies suggested that a considerable decrease in the release rate or an increase in partition coefficient (experimentally more than 10(8) would be required for delivery.
在荷瘤大鼠中研究了水包油（O/W）脂质乳剂作为亲脂性药物胃肠外给药系统的潜在用途。一种模型亲脂性药物苏丹II（正辛醇/水分配系数=226000）被制成由大豆油和各种表面活性剂组成的五种脂质乳剂。与苏丹II的HCO - 60胶束溶液和血浆溶液相比，以脂质乳剂形式给药后，苏丹II的血药浓度显著升高。然而，苏丹II在肝脏、肺、脾脏和脂肪组织中的分布没有改变，而在脑、心脏、肾脏、肌肉和肿瘤中的分布略有减少。为了解这些结果，使用新推导的房室模型进行了药代动力学分析，此外，还分析了器官分布清除率。结果表明，油颗粒将包封的药物选择性地输送到肝脏、肺和脾脏，并且使用HCO - 60可以抑制输送速度。然而，对于苏丹II，静脉注射后其从油颗粒中的快速释放阻止了苏丹II分布的剧烈改变。模拟研究表明，为了实现药物输送，释放速率需要大幅降低或分配系数需要增加（实验上大于10^8）。
