Pharmacokinetics of azathioprine following single-dose intravenous and oral administration and effects of azathioprine following chronic oral administration in horses.

The research is about studying the pharmacokinetics and effects of azathioprine (AZA), a drug administered to horses, and if it has any short or long term adverse effects. It focuses on determining the behavior of the drug within the body of the horses through intravenous (IV) and oral administration, with all indications pointing to low chances of adverse effects.

Study Design and Methodology

• The study was done in two separate phases. Six horses were used for the experiment.
• In the first phase, a single dose of azathioprine was administered either intravenously (1.5mg/kg) or orally (3.0mg/kg) to the horses, with a minimum of one week between the two treatments.
• Blood samples were then collected 1 hour before and at certain time intervals up to 4 hours following the administration of AZA. These samples were analysed for AZA and 6-mercaptopurine (6-MP), a metabolite of AZA.
• In the second phase, AZA was administered orally daily (3mg/kg) for 30 days and then every 48 hours for an additional 30 days. Regular blood samples were taken for Complete Blood Count (CBC) determination and serum biochemical analysis.

Research Findings

• The study found that the plasma concentrations of azathioprine and its metabolite decreased rapidly after it was administered intravenously. This aligns with the drug’s short mean elimination half-life of about 1.8 minutes.
• The oral bioavailability of azathioprine, which is the proportion of the drug that enters circulation when introduced in the body and so is able to have an active effect, was quite low. It ranged from 1% to 7% of the administered dose.
• No abnormal results were found in the blood count determination or the serum biochemical analysis for all horses, except for one horse which exhibited lymphopenia on day 5 and 26 of the daily treatment.
• Noteably, this lymphopenic horse developed a facial hair loss condition, from which a Trichophyton sp fungal colony was cultured. However, this condition got resolved within a month of ending the study.

Conclusions and Implications

• The research concluded that, overall, there were no adverse effects observed with the long-term oral administration of azathioprine to the horses.
• Just one horse showed potential signs of immunosuppression with chronic treatment.
• Given these findings, further exploration into the clinical effectiveness of azathioprine in treating autoimmune diseases in horses is highly recommended.