Tibell A, Norrlind B
Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Sweden.
Transpl Int. 1994;7(6):438-41. doi: 10.1007/BF00346039.
Cyclosporin A (CyA) is an extremely lipophilic drug that needs a solubilizing agent to become soluble in water. In the commercially available intravenous formulation--Sandimmun--Cremophor EL is used for this purpose. It is likely that Cremophor EL contributes to some of the side effects produced by i.v. Sandimmun. We have recently shown that if Cremophor EL is replaced by a soybean oil (SBO)-based fat emulsion carrier, the acute renal side effects following i.v. administration of CyA are avoided in a rat model. It is then important to ascertain whether the use of a fat emulsion carrier alters the immunosuppressive effect of CyA. Moreover, fatty acids can themselves influence the immune system, and both omega-3 and omega-6 fatty acids have been reported to possess immunosuppressive properties. In the present study, the effect on graft survival of i.v. CyA administered in five different formulations, using fat emulsions or liposomes as carriers, was compared to that of conventional Sandimmun infusion substance in the heterotopic heart transplant model in rats. The new formulations tested did not reduce the immunosuppressive effect of CyA. On the contrary, a small but significant increase in graft survival was noted in the groups given CyA in the SBO-based fat emulsion carrier (17.0 +/- 0.82 days) and CyA in liposomes (16.0 +/- 0.63 days) as compared to the results in the Sandimmun-treated group (15.0 +/- 0.58 days: P < 0.01 and P < 0.05, respectively).
环孢素A（CyA）是一种极亲脂性药物，需要增溶剂才能溶于水。在市售的静脉制剂——山地明（Sandimmun）中，聚氧乙烯蓖麻油（Cremophor EL）被用于此目的。聚氧乙烯蓖麻油很可能导致了静脉注射山地明产生的一些副作用。我们最近发现，如果用基于大豆油（SBO）的脂肪乳剂载体替代聚氧乙烯蓖麻油，在大鼠模型中静脉注射环孢素A后的急性肾副作用可避免。因此，确定使用脂肪乳剂载体是否会改变环孢素A的免疫抑制作用很重要。此外，脂肪酸本身会影响免疫系统，据报道，ω-3和ω-6脂肪酸都具有免疫抑制特性。在本研究中，将以脂肪乳剂或脂质体为载体的五种不同制剂静脉注射环孢素A对大鼠异位心脏移植模型中移植物存活的影响与传统山地明输注物质的影响进行了比较。所测试的新制剂并未降低环孢素A的免疫抑制作用。相反，与山地明治疗组（15.0±0.58天）相比，给予基于大豆油脂肪乳剂载体的环孢素A组（17.0±0.82天）和脂质体中环孢素A组（16.0±0.63天）的移植物存活时间有小幅但显著的增加（分别为P<0.01和P<0.05）。
