title: Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction.
abstract: METHODS
  Laboratory investigation in rats submitted to experimental spinal cord injury (SCI).
  
  
  OBJECTIVE
  To determine the effect of acute SCI on the pharmacokinetics of diclofenac, a marker drug of intermediate hepatic extraction, administered by the intravenous and the oral routes.
  
  
  METHODS
  Female Wistar rats were submitted to complete section of the spinal cord at the T8 level. SCI and sham-injured rats received 3.2 mg kg(-1) of diclofenac sodium either intravenously or orally, diclofenac concentration was measured in whole blood samples and pharmacokinetic parameters were estimated. Diclofenac was not selected as test drug because of its therapeutic properties, but because to its biopharmaceutical properties, that is, intermediate hepatic extraction.
  
  
  RESULTS
  Diclofenac bioavailability after intravenous administration was increased in injured rats compared with controls due to a reduced clearance. In contrast, oral diclofenac bioavailability was diminished in SCI animals due to a reduction in drug absorption, which overrides the effect on clearance.
  
  
  CONCLUSIONS
  Acute SCI induces significant pharmacokinetic changes for diclofenac, a marker drug with intermediate hepatic extraction. SCI-induced pharmacokinetic changes are not only determined by injury characteristics, but also by the route of administration and the biopharmaceutical properties of the studied drug.
authors.affiliation: Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, México, DF, México.
authors.forename: L
authors.initials: L
authors.lastname: Cruz-Antonio
authors.forename: J
authors.initials: J
authors.lastname: Arauz
authors.forename: R E
authors.initials: RE
authors.lastname: Franco-Bourland
authors.forename: G
authors.initials: G
authors.lastname: Guízar-Sahagún
authors.forename: G
authors.initials: G
authors.lastname: Castañeda-Hernández
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004008:Diclofenac / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D004008:Diclofenac