Canagliflozin: Pharmacokinetics, tolerability and glucose/insulin effects of supratherapeutic doses in healthy horses.

The research studies the drug canagliflozin and its effects on glucose and insulin in healthy horses. Researchers found that the drug could effectively control glucose and insulin levels without causing significant adverse effects.

Background

• The drug canagliflozin (CFZ) is a inhibitor of the Sodium-glucose co-transporter 2 (SGLT2) pathway, known for its role in treating diabetes in humans. Recent studies indicate it may prevent hyperinsulinemia-associated laminitis, a painful condition affecting the legs of horses.
• However, data about CFZ’s effects in horses is limited, particularly in terms of pharmacokinetics (how the drug moves through the body), tolerability, and controlled studies.

Methods

• To fill this gap in knowledge, the researchers conducted a randomized, open-label, placebo-controlled crossover study using eight healthy Standardbred mares.
• Each horse was administered single doses of CFZ higher than the usual therapeutic dosage (1.8 mg/kg or 3.6 mg/kg) and placebo, with a two-week interval between treatments.
• To evaluate the response to glucose and insulin, a graded glucose infusion (GGI) was given after each treatment.
• The researchers also took samples of plasma and urine over 72 hours following treatment to monitor CFZ, glucose, insulin levels in the bloodstream and urinary glucose.

Findings

• The findings showed that the concentrations of CFZ in the bloodstream increased proportionally with the dosage. Similarly, the time for the drug to reach peak concentration (T) and the time for half the drug to be eliminated from the body (T) also rose slightly with increase in dosage.
• The drug significantly reduced the insulin and glucose responses to the GGI, compared to the placebo: glucose levels went down by around 14-15% and insulin levels by around 22-29%.
• In respect to urinary glucose concentrations, they ranged from 277 to 347 mmol/L at 24, 48, and 72 hours after drug administration, with no significant variation between dose levels.

Conclusions

• No significant adverse effects were observed in the horses, except for a notable increase in the liver enzyme GLDH, when given the larger dose of 3.6 mg/kg. It suggests that caregivers should monitor the liver status of horses under the given dosage.
• Overall, the study indicates canagliflozin as a promising treatment to control glucose and insulin levels in horses, which could prevent conditions like laminitis and improve their quality of life.