In recent years, the detection of metformin in blood and urine samples collected from racehorses has raised concern among regulators. This study describes blood and urine concentrations and the pharmacokinetics of metformin following IV and oral administration to horses. Data presented here can be used to establish screening limits and withdrawal times to appropriately regulate this drug in performance horses.

ABSTRACT

The racehorse industry has strict regulations regarding the detection of prohibited substances in horses. Metformin, a diabetes medication, is a prohibited substance that has been reported in post-race blood and urine samples collected from racehorses. For further characterization of the disposition of metformin, 12 Thoroughbred horses were administered metformin orally and intravenously in a randomized, balanced, two-way crossover design. Serum and urine samples were collected, and drug concentrations determined via liquid chromatography–tandem mass spectrometry. The serum data were analyzed using both noncompartmental analysis and a population pharmacokinetic model. Metformin concentrations were below the LOQ (0.25 ng/mL) in six of 12 horses by Day 11 postadministration, and below the LOQ for all horses on Day 25. The maximum serum concentration of metformin (mean ± SD) was 941.0 ± 467.8 ng/mL, and the mean terminal t_1/2 was 85.8 ± 15.1 h. Based on Monte Carlo simulations the time that serum metformin concentrations fell below the proposed HISA Anti-Doping and Medication Control (ADMC) minimum reporting level (MRL; 0.5 ng/mL) in a simulated population of 1000 Thoroughbred horses was 475 hrs (~20 days). Metformin concentrations in urine fluctuated significantly between and within individual horses, and there was not a consistent relationship between blood and urine samples across time points. Results of the present study demonstrate a prolonged detection time; thus, a prolonged withdrawal time is needed to prevent a positive finding following exposure to metformin. Additionally, these results suggest that blood is the preferred matrix for regulatory purposes due to the inconsistent elimination in urine.