Department of Surgical Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Pharm Sci. 2011 Jul;100(7):2685-92. doi: 10.1002/jps.22488. Epub 2011 Jan 18.
The purpose of this study was to evaluate the effectiveness of a novel fluorocarbon-based sevoflurane emulsion in dogs previously shown to produce short-term rodent anesthesia. On the basis of an unexpected allergic-type clinical reaction, we also tested the hypothesis that this type of formulation causes histamine release and complement activation. Physiological parameters, plasma histamine levels (radioimmunoassay), and complement activation (enzyme immunoassay) were quantified in response to emulsion components, including F13M5 (the emulsion's fluorocarbon-based polymer) and methoxy poly(ethylene glycol) 5000 (the polymer's hydrophilic block). Although the emulsion produced general anesthesia in dogs, they also experienced hypotension and clinical signs suggestive of an allergic-like response (i.e., vasodilation, urticaria, and pruritus upon recovery). Emulsions lacking sevoflurane failed to induce anesthesia but did elicit the allergic response. Plasma histamine levels were significantly increased following injection of micellar solutions of F13M5. Direct complement activation by the emulsion or its components was weak or absent. An allergic response leading to histamine release, likely initiated by the F13M5 component via an immunoglobulin pathway, is associated with an intravenous fluorocarbon-based emulsion of sevoflurane. Subsequently, its usefulness in medicine in its present formulation is limited.
本研究旨在评估一种新型氟碳基七氟醚乳剂在先前已被证明可产生短期啮齿动物麻醉的犬中的效果。基于一种意外的过敏样临床反应，我们还测试了以下假设，即这种制剂会引起组胺释放和补体激活。通过放射免疫测定法测定生理参数、血浆组胺水平（放射免疫测定法）和补体激活（酶免疫测定法），以响应乳剂成分，包括 F13M5（乳剂的基于氟碳的聚合物）和甲氧基聚（乙二醇）5000（聚合物的亲水性嵌段）。尽管乳剂可使犬产生全身麻醉，但它们也经历了低血压和临床症状，提示过敏样反应（即血管扩张、荨麻疹和恢复时瘙痒）。缺乏七氟醚的乳剂无法诱导麻醉，但会引发过敏反应。注射 F13M5 的胶束溶液后，血浆组胺水平显著升高。乳剂或其成分的直接补体激活较弱或不存在。与 F13M5 成分通过免疫球蛋白途径引发的组胺释放相关的过敏反应与静脉内氟碳基七氟醚乳剂有关。随后，其在当前制剂中的医学用途受到限制。
