Ibarra A, Reyes J, Martínez S, Correa D, Guízar-Sahagún G, Grijalva I, Castañeda-Hernández G, Flores-Murrieta F J, Franco-Bourland R, Madrazo I
Proyecto CAMINA, A.C., México, D.F.
J Neurotrauma. 1996 Oct;13(10):569-72. doi: 10.1089/neu.1996.13.569.
Cyclosporin-A (CsA) is frequently used as an immunosuppressive agent in experimental transplantations. CsA has been used in nervous tissue transplants in spinal cord injury (SCI). However, optimal results have not been obtained. This is likely due to the fact that SCI alters CsA pharmacokinetics and hence fixed dose regimens are not adequate. In this study, several CsA dosing regimens were evaluated in Long-Evans female rats subjected to a severe low thoracic (T8) SCI by the contusion method. Serum CsA concentrations were measured to determine which dosing regimen allowed CsA levels to be maintained within the therapeutic window. It was found that administration of 2.5 mg/kg/12 h intraperitoneally during the first 2 days after SCI (acute phase) followed by 5 mg/kg/12 h orally thereafter (subacute and chronic phases) yields CsA circulating levels within the therapeutic window, i.e., 0.120-0.275 microgram/mL. This dosing regimen represents a suitable alternative to fixed dosing to achieve an optimal CsA-induced immunosuppression in experimental models of SCI.
环孢素A（CsA）在实验性移植中常被用作免疫抑制剂。CsA已用于脊髓损伤（SCI）的神经组织移植。然而，尚未获得最佳效果。这可能是因为SCI改变了CsA的药代动力学，因此固定剂量方案并不合适。在本研究中，对采用挫伤法造成严重胸段低位（T8）SCI的Long-Evans雌性大鼠评估了几种CsA给药方案。测量血清CsA浓度以确定哪种给药方案能使CsA水平维持在治疗窗内。结果发现，在SCI后的头2天（急性期）腹腔注射2.5mg/kg/12h，此后（亚急性期和慢性期）口服5mg/kg/12h，可使CsA循环水平维持在治疗窗内，即0.120 - 0.275微克/毫升。这种给药方案是在SCI实验模型中实现最佳CsA诱导免疫抑制的固定给药的合适替代方案。
