Disposition, bioavailability and clinical efficacy of orally administered acepromazine in the horse.

This research examined how efficiently the drug acepromazine, used as a sedative for horses, is absorbed and functions when given orally in comparison to intravenous administration. The findings indicated that the drug’s absorption and elimination rates differed between the two methods of administration, and side effects were less pronounced with oral administration.

Objective and Methodology

• The primary objective of the research was to compare the efficiency of orally administered acepromazine (a widely used sedative in equine patients) to its intravenous administration.
• This was achieved by studying the pharmacokinetics – how the drug is absorbed, distributed, metabolized, and excreted in the body – and pharmacological efficacy, which assesses the therapeutic effects of the drug.
• Six horses were used in a cross-over study design, a type of longitudinal study in which subjects receive a sequence of different treatments. This facilitates direct comparison of different treatments administered to the same individual.

Findings

• Acepromazine, when given orally, was rapidly absorbed into the body with a half-life of 0.84 hours, reaching its maximum concentration (Cmax) of 59 ng/ml at about 0.4 hours (tmax) after administration.
• The rate at which the drug was eliminated from the body was slower for oral administration (half-life 6.04 hours) compared to intravenous administration (half-life 2.6 hours).
• The oral bioavailability – the proportion of the drug that enters the circulation when introduced orally and so can have an active effect – was 55.1%. This implies that nearly half the drug might be lost during the digestion process, reducing the overall efficacy of the drug when administered orally.

Sedative Effect and Side Effects

• After administration of 0.5 mg/kg acepromazine orally, the parameters of sedative effect were similar to those obtained after intravenous injection of 0.1 mg/kg.
• The effects on blood count and haemoglobin content, an indication of oxygen-carrying capacity in the blood, were comparable for both oral administration and intravenous injection.
• Effects on penile prolapse (a common side effect of acepromazine in males) and mean arterial blood pressure were less pronounced after oral administration compared to injection.
• No significant effects on haematocrit level (percentage of red blood cells in blood), heart rate, and respiratory rates were observed after oral administration, whereas these parameters were significantly affected after injection.
• This suggests that oral administration of acepromazine can minimize potential adverse side effects that may occur from intravenous administration.

Conclusion

• The researchers concluded that the more immediate and concentrated introduction of the drug to the bloodstream via intravenous injection might lead to higher initial plasma levels, potentially causing more pronounced side effects. Hence, oral administration could be a safer, although slightly less efficient, alternative for sedation in horses.