Affiliations: Department of Physical Medicine and Rehabilitation,
University of Minnesota, Minneapolis, MN, USA | Department of Pediatrics, University of Minnesota,
Minneapolis, MN, USA | Department of Neurology, University of Minnesota,
Minneapolis, MN, USA | Department of Veterinary Clinical Sciences, University
of Minnesota, Minneapolis, MN, USA | Department of Experimental and Clinical Pharmacology,
University of Minnesota, Minneapolis, MN, USA | Center for Orphan Drug Research, University of
Minnesota, Minneapolis, MN, USA
Note: [] Corresponding author: Linda E. Krach, MD, Department of Physical
Medicine and Rehabilitation, University of Minnesota Medical School, Mayo Mail
Code 297, 420 Delaware Street SE, Minneapolis, MN 55455, USA. Tel.: +1 612 626
5578; Fax: +1 612 624 6686; E-mail: krach002@umn.edu
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.
