TY - JOUR
T1 - Alteration of cyclosporin-A pharmacokinetics after experimental spinal cord injury
AU - Ibarra, Antonio
AU - Guízar-Sahagún, Gabriel
AU - Correa, Dolores
AU - Kretschmer, Roberto
AU - Grijalva, Israel
AU - Flores-Murrieta, Francisco J.
AU - Castañeda-Hernández, Gilberto
AU - Odor, Alberto
AU - López, Rosa M.
AU - Franco-Bourland, Rebecca
AU - Espitia, Ana L.
AU - Salgado-Ceballos, Hermelinda
AU - Madrazo, Ignacio
PY - 1996/5
Y1 - 1996/5
N2 - 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.
AB - 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.
KW - bioavailability
KW - cyclosporin-A
KW - immunosuppressive agents
KW - neural transplantation
KW - paraplegia
KW - pharmacokinetics
KW - spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=15844395462&partnerID=8YFLogxK
U2 - 10.1089/neu.1996.13.267
DO - 10.1089/neu.1996.13.267
M3 - Artículo
C2 - 8797176
AN - SCOPUS:15844395462
SN - 0897-7151
VL - 13
SP - 267
EP - 272
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 5
ER -