Evaluation of the pharmacokinetics and bioavailability of intravenously and orally administered amiodarone in horses.

This research explores how the drug amiodarone, when given to horses intravenously or orally, is distributed, metabolized, and cleared from the body. No adverse effects were observed. Results indicate that the distribution of amiodarone throughout the body is complex, it does not get excreted via the kidneys, and has low uptake after oral administration.

Study Design

• This research was a crossover study conducted on 6 healthy adult horses. A crossover study is a type of clinical trial where the subjects serve as their own control group. This is to limit the effects of confounding variables.
• Each horse was administered a single dose of 5 mg/kg of amiodarone, either orally or intravenously.
• The researchers monitored the horses for any clinical signs and also checked their electrocardiographic variables.
• Plasma and urine samples were collected at different points in time for further analysis.

Methods of Data Collection

• The researchers used a method known as liquid chromatography-mass spectrometry to determine the percentage of protein binding and to measure the levels of amiodarone and its active metabolite desethylamiodarone in the plasma and urine samples.

Results

• No adverse clinical signs were observed in any of the horses after the administration of amiodarone.
• After intravenous administration, the median terminal half-life (the time taken for the drug concentration to decrease by half) of amiodarone was 51.1 hours, and for desethylamiodarone, it was 75.3 hours.
• The clearance rate of the drug (rate at which a drug is removed from the body) was found to be 0.35 L/kg x h.
• The apparent volume of distribution (how widely the drug spreads throughout the body) was 31.1 L/kg for amiodarone.
• The peak plasma concentration of desethylamiodarone was achieved 2.7 hours after intravenous administration.
• Both the parent drug amiodarone and its metabolite desethylamiodarone were not detected in the urine samples which implies that they might not be eliminated through the kidneys.
• On the other hand, after oral administration, the absorption of amiodarone was slow and variable with a low bioavailability range of 6.0% to 33.7%.
• The peak plasma concentration of amiodarone and desethylamiodarone was attained 7.0 hours and 8.0 hours after administration, respectively.
• Amiodarone was found to be highly protein-bound (96%), which means it mostly attaches to proteins in the blood, affecting how it is distributed, stored, and eliminated.

Conclusions

• The distribution of amiodarone in the body is multicompartmental, suggesting a complex interaction with various tissues and compartments in the body.
• The finding that amiodarone has low bioavailability after oral administration and does not undergo renal excretion is significant, as it impacts the effectiveness of oral dosing and informs the excretion pathway of the drug.
• This information is crucial for determining the most effective treatment regimens for horses diagnosed with arrhythmias.