Clinical tolerance and toxicity of intravenous baclofen: A pilot study in a canine model

Linda E. Krach, Robert L. Kriel, Ned Patterson, Lisa A. Scherkenbach, Lisa D Coles, James C Cloyd

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Objective: Assess safety and tolerance of intravenous (IV) baclofen using a dog model. Design: 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.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalJournal of Pediatric Rehabilitation Medicine
Volume4
Issue number2
DOIs
StatePublished - 2011

Keywords

  • Baclofen
  • dogs
  • muscle spasticity
  • pharmacokinetic

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