Alteration of cyclosporin-A pharmacokinetics after experimental spinal cord injury

Antonio Ibarra, Gabriel Guízar-Sahagún, Dolores Correa, Roberto Kretschmer, Israel Grijalva, Francisco J. Flores-Murrieta, Gilberto Castañeda-Hernández, Alberto M Odor, Rosa M. López, Rebecca Franco-Bourland, Ana L. Espitia, Hermelinda Salgado-Ceballos, Ignacio Madrazo

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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 (ip) or orally to rats submitted to experimental SC injury at the T8 level. Twenty four hours after lesion (acute stage of SC injury) ip CsA bioavailability was increased, while t(1/2) 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.

Original languageEnglish (US)
Pages (from-to)267-272
Number of pages6
JournalJournal of Neurotrauma
Volume13
Issue number5
StatePublished - May 1996
Externally publishedYes

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Keywords

  • bioavailability
  • cyclosporin-A
  • immunosuppressive agents
  • neural transplantation
  • paraplegia
  • pharmacokinetics
  • spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Ibarra, A., Guízar-Sahagún, G., Correa, D., Kretschmer, R., Grijalva, I., Flores-Murrieta, F. J., Castañeda-Hernández, G., Odor, A. M., López, R. M., Franco-Bourland, R., Espitia, A. L., Salgado-Ceballos, H., & Madrazo, I. (1996). Alteration of cyclosporin-A pharmacokinetics after experimental spinal cord injury. Journal of Neurotrauma, 13(5), 267-272.