title: Clinical tolerance and toxicity of intravenous baclofen: a pilot study in a canine model.
abstract: OBJECTIVE
  Assess safety and tolerance of intravenous (IV) baclofen using a dog model.
  
  
  METHODS
  Prospective pharmacokinetic study involving 6 adult dogs. Two dogs received baclofen 10 mg oral and IV bolus doses. Subsequent 4 dogs were given IV boluses of 0.5, 1.0 and 1.5 mg/kg followed by constant infusion of baclofen (rates of 0.1, 0.2 and 0.4 mg/kg/hour). Also, dogs were given single IV 2 and 3 mg /kg bolus doses. Outcome measures included clinical observation scales and baclofen levels.
  
  
  RESULTS
  Oral bioavailability was 0.66 and 0.69 in 2 dogs. Following IV baclofen, terminal phase half-lives were 3.3 and 3.6 hours. Single bolus doses of 2 and 3 mg/kg caused mild to moderate clinical changes which were delayed at least 2 hours after peak blood levels. Boluses of 0.5 and 1.0 mg/kg with constant infusion between boluses were tolerated, however within 30 minutes of beginning constant infusion of 0.2 mg/kg/hr after the second bolus (1.0 mg/kg), dogs showed progressive sedation and ataxia. Clinical improvement occurred within 7 hours of stopping baclofen. Dogs appeared normal by the next morning.
  
  
  CONCLUSIONS
  IV baclofen bolus doses of 0.5 to 3 mg/kg were well tolerated. Maximum clinical effect was delayed for at least 2 hours after peak plasma levels.
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN 55455, USA. krach002@umn.edu
authors.forename: Linda E
authors.initials: LE
authors.lastname: Krach
authors.forename: Robert L
authors.initials: RL
authors.lastname: Kriel
authors.forename: Edward E
authors.initials: EE
authors.lastname: Patterson
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Scherkenbach
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Coles
authors.forename: James C
authors.initials: JC
authors.lastname: Cloyd
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D004285:Dogs; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D023421:Models, Animal; D009125:Muscle Relaxants, Central / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D009125:Muscle Relaxants, Central; D001418:Baclofen