Metformin in the Horse: Pharmacokinetic Modeling, Detection Methods, and Environmental Exposure
Abstract
The horseracing industry has strict regulations regarding the presence of chemical substances in equine athletes at the time of competition. Metformin, a commonly prescribed diabetes medication in human medicine, is considered a prohibited substance in horseracing, as there is no accepted therapeutic use for this compound in young, fit horses. Recent metformin detections in post-race blood and urine samples resulting in adverse analytical findings and severe disciplinary action against the trainers of the horses involved necessitates further study of this drug in horses. This thesis aims to characterize the pharmacokinetic behavior of metformin in the horse and explore environmental contamination as a means of exposure to inform regulation of metformin in horseracing.In the first study, a pharmacokinetic (PK) study of metformin was performed utilizing twelve horses. Metformin was administered orally and intravenously in a balanced, randomized, two-way crossover design. Serum drug concentrations were determined using a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and data was analyzed via noncompartmental analysis (NCA) for calculation of select pharmacokinetic parameters. Subsequently, concentrations were analyzed using a non-linear mixed effects (NLME) population model. The final model was then used to perform Monte Carlo simulations utilizing the estimated fixed effects and interindividual variability of the study horses to generate…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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