Ibarra A, Guízar-Sahagún G, Correa D, Kretschmer R, Grijalva I, Flores-Murrieta F J, Castañeda-Hernández G, Odor A, López R M, Franco-Bourland R, Espitia A L, Salgado-Ceballos H, Madrazo I
Proyecto CAMINA A.C., México, D.F., Mexico.
J Neurotrauma. 1996 May;13(5):267-72. doi: 10.1089/neu.1996.13.267.
The pharmacokinetics of the immunosuppressive agent cyclosporin-A (CsA) were studied in rats submitted to spinal cord (SC) injury. A single CsA 10 mg/kg dose was given either intraperitoneally (i.p.) or orally to rats submitted to experimental SC injury at the T8 level. Twenty four hours after lesion (acute stage of SC injury) i.p. CsA bioavailability was increased, while t1/2 was prolonged. However, oral bioavailability was reduced. Seven weeks after lesion (chronic stage of SC injury) CsA bioavailability, by either route, was not significantly different from control values. Results indicate that parenteral CsA bioavailability is increased during the acute stage of SC lesion, probably due to an impaired elimination. Oral bioavailability, however, is decreased, since there is also an important reduction in gastrointestinal CsA absorption that overrides the effect of impaired elimination. Alterations in CsA pharmacokinetics appear to revert during the chronic stage of SC injury. Changes in CsA bioavailability, depending on the route of administration and on time, must be considered to design an adequate immunosuppressive treatment in SC injury.
在遭受脊髓（SC）损伤的大鼠中研究了免疫抑制剂环孢素A（CsA）的药代动力学。给T8水平遭受实验性SC损伤的大鼠腹腔内（i.p.）或口服单次10 mg/kg剂量的CsA。损伤后24小时（SC损伤急性期），腹腔注射CsA的生物利用度增加，而半衰期延长。然而，口服生物利用度降低。损伤后7周（SC损伤慢性期），无论何种给药途径，CsA的生物利用度与对照值无显著差异。结果表明，在SC损伤急性期，肠外CsA的生物利用度增加，可能是由于消除受损。然而，口服生物利用度降低，因为胃肠道CsA吸收也有重要减少，超过了消除受损的影响。CsA药代动力学的改变在SC损伤慢性期似乎恢复。在设计SC损伤的适当免疫抑制治疗时，必须考虑CsA生物利用度根据给药途径和时间的变化。
