Amantadine and equine influenza: pharmacology, pharmacokinetics and neurological effects in the horse.

The research article explores the effectiveness, detection, disposal, modeling, and possible side effects of the antiviral agent Amantadine in treating equine influenza. The study focused on two compounds – Amantadine and its derivative Rimantadine, and concluded that while both can suppress the virus, Rimantadine was more effective. However, administration of Amantadine has to be careful, as excessive dosing leads to seizures in horses.

Antiviral Efficacy and Analytical Detection

• The researchers examined the antiviral efficacy of Amantadine and its derivative Rimantadine against equine-2 influenza virus.
• Both compounds suppressed the replication of the virus with effective doses of less than 30 ng/ml.
• Rimantadine proved to be more effective against most of the viral isolates studied.

Bioavailability and Disposition

• In terms of bioavailability, the researchers suggest a minimum plasma concentration of 300 ng/ml of amantadine for therapeutic efficacy.
• Following an intravenous (IV) dose of 15 mg/kg body weight (bwt) of amantadine, horses exhibited mild, transient central nervous system (CNS) signs which disappeared after 30 minutes.
• This study determined 15 mg/kg bwt as the maximum safe single IV dose. However, if repeated IV administration is necessary, no more than 10 mg/kg bwt should be used three times a day.

Pharmacokinetic Modelling

• The discharge kinetics of amantadine, when administered via IV at a dosage of 10 mg/kg bwt, were accurately modelled by a 2-compartment open model.
• The estimated peak plasma concentration at this dose was about 4500 ng/ml.
• The volume of distribution at steady-state (Vdss) was 4.9 +/- 1.9 l/kg bwt, and the beta phase half-life was 1.83 +/- 0.87 hours.

Adverse Reactions and Safety Thresholds

• The study noted that horses with lower seizure thresholds or those on medications that lower seizure thresholds may be at increased risk of amantadine-induced seizures, which show very few premonitory signs and can be rapidly fatal.
• Therefore, care should be taken to ensure that the seizure threshold is not exceeded during administration of amantadine.
• In acute situations, IV administration (5 mg/kg bwt) every 4 hours should maintain safe and effective plasma and respiratory tract concentrations of amantadine.

Bioavailability Variations and Oral Administration

• When amantadine was given orally at 10 mg/kg bwt and 20 mg/kg bwt, it showed a mean oral bioavailability of about 40-60% and a plasma half-life of 3.4 +/- 1.4 hours.
• However, a substantial variation in bioavailability was observed between different animals. Some animals were able to maintain effective plasma concentrations of amantadine after oral administration of 20 mg/kg bwt thrice a day.
• Animals in which amantadine was poorly bioavailable may require up to a 6-fold (120 mg/kg bwt) increase in the oral dose to achieve effective blood concentrations.
• The researchers found that withholding food for 15 hours did not affect these inter-animal differences in bioavailability. As a result, a simple oral dose of amantadine won’t yield effective plasma concentrations in all animals.