Pharmacokinetics and pharmacodynamics of intravenous baclofen in dogs: a preliminary study†

Abstract

Abrupt discontinuation of baclofen therapy is associated with a clinically serious withdrawal syndrome. Current treatment modalities are often ineffective. Intravenous (IV) baclofen is a potential method for preventing or treating baclofen withdrawal syndrome. To complete a preliminary study of IV baclofen in dogs. Single bolus IV doses (0.5, 2 and 3 mg/kg) as well as multiple dose regimens were evaluated. Sedation and clinical tolerability was assessed by modified Glasgow Coma Scale and Discomfort and Behaviour Scale. Baclofen concentration-time profiles following single IV boluses were best fit by a two-compartment model which was used to predict plasma concentrations for the multiple dose regimens. The mean distribution and elimination half-lives were 11 min and 222 min, respectively. Maximum clinical effect did not occur until approximately 120 min. The discomfort score increased proportionately with increased single IV bolus doses. Multiple dose regimens resulted in greater than proportionate discomfort scores based on total dose and were generally not as well tolerated. If projected for human use, our data suggests that initial IV baclofen doses will need to be reduced by approximately one-third of the usual oral dose, and clinicians should observe patients for several hours before administering subsequent doses.