Long-term intraventricular baclofen infusion in beagles

Area of Science:

• Neuroscience
• Pharmacology
• Veterinary Medicine

Background:

• Intraventricular baclofen infusion is a potential therapeutic strategy.
• Understanding the long-term safety profile is crucial for clinical application.

Purpose of the Study:

• To evaluate the clinical and histopathological effects of 3-month intraventricular baclofen infusion in beagle dogs.
• To determine the dose-limiting toxicity of intraventricular baclofen in a preclinical model.

Main Methods:

• Stereotactic catheter placement into lateral ventricles of beagle dogs.
• Continuous infusion of saline (control) or intraventricular baclofen (IVB) via implanted pumps.
• Dosages of IVB ranged from 100 to 1000 µg/day over a 3-month period.

Main Results:

• No adverse effects were observed with IVB infusion at 135 µg/day or less for 3 months.
• Dosages of 150 µg/day led to seizures and adverse effects, which resolved upon dose reduction.
• Higher IVB dosages (250-1000 µg/day) resulted in lethal toxicity within 4 days.
• Histopathology revealed no significant changes at tolerated IVB dosages.

Conclusions:

• Intraventricular baclofen exhibits dose-dependent toxicity in beagles.
• Clinically relevant dosages (≤135 µg/day) of IVB were well-tolerated over 3 months without clinical or neurological toxicity.
• This study establishes a safe dosage range for long-term IVB infusion in preclinical settings.