The pharmacokinetics or oral and intravenous allopurinol and intravenous oxypurinol in the horse.

The study explores how the drug allopurinol, administered both orally and intravenously, and its active metabolite oxypurinol, given intravenously, behave in the bodies of horses with regards to concentration over time and bioavailability, and provides an understanding of allopurinol’s metabolism to oxypurinol.

Research Methodology and Process

• The experiment involved five horses to understand the pharmacokinetics – the study of how a drug is absorbed, distributed, metabolized, and excreted by an organism – of allopurinol and oxypurinol.
• The research progressed by administering the horses with oral and intravenous allopurinol and comparing it with intravenous oxypurinol.
• In this experiment, administration of 5mg/kg of intravenous allopurinol and oxypurinol was followed by monitoring and recording the plasma concentration against time.
• The plasma concentration over time for the drugs in the horse bodies were best described using biexponential equations.

Findings and Results

• The elimination half-life, which refers to the time taken for a substance concentration to decrease by half in the body, for allopurinol was found to be 0.09 hours with an area under the curve (AUC) of 19.8 mumol.h/L after intravenous administration. This data gives a measure of the drug exposure over time.
• Comparatively, the elimination half-life and AUC for oxypurinol were 1.09 hours and 231 mumol.h/L respectively, showing that oxypurinol stays in the body longer and has greater exposure than allopurinol.
• The oral bioavailability, or the proportion of the drug that enters the circulation when introduced into the body, of allopurinol was found to be low at 14.3%. Two of the horses even showed no trace of the drug in the plasma after oral administration.
• Interestingly, the study found that orally administered allopurinol was equivalent to intravenous oxypurinol, which suggests allopurinol is quickly metabolized into oxypurinol in the body.

Implications of the Research

• The results suggested that allopurinol is rapidly metabolized into oxypurinol in the horse.
• The majority of the pharmacological activity of allopurinol in the horse may happen through the action of the metabolite, oxypurinol. This could be relevant in designing future dosing strategies and understanding how to maximize the therapeutic benefits of allopurinol in horses.