What question did this study set out to answer?

This study aims to evaluate how metformin is sequestered in red blood cells and its effects on the drug's pharmacokinetics in horses.

April 18, 2026Open Access

Erythrocyte sequestration of metformin in horses: impact on matrix-specific pharmacokinetics and detection windows

Key Points

This study aims to evaluate how metformin is sequestered in red blood cells and its effects on the drug's pharmacokinetics in horses.
Administered a single 15 g oral dose of metformin to six horses.
Collected plasma, serum, whole blood, red blood cells, and urine samples from 5 min to 31 days post-administration.
Determined metformin concentrations using liquid chromatography-tandem mass spectrometry.
Conducted pharmacokinetic analysis on collected samples.
Red blood cells serve as a significant reservoir for metformin.
The average blood to plasma ratio was observed to range from < 1 to > 10 at later time points.
The terminal half-lives in plasma, serum, and red blood cells were 14.7 ± 7.25, 75.4 ± 32.2, and 49.1 ± 7.01 hours respectively.
There were notable differences (> 15%) between serum and plasma concentrations at several time points.
Urine concentrations of metformin fluctuated unpredictably, complicating detection.

Abstract

Metformin is used for the treatment of type 2 diabetes and is one of the most prescribed medications in human medicine. It is less commonly prescribed in equine medicine, and its use is tightly regulated in several performance horse disciplines. In horseracing, it is considered a banned substance. A previous pharmacokinetic study of metformin in horses demonstrated a prolonged, unpredictable elimination phase. In the current study it was hypothesized that this was due to sequestration of metformin in a “deep” compartment, specifically red blood cells. This could result in pharmacokinetic differences between blood matrices (i.e. blood and serum). The objective of the current study was to assess red blood cell partitioning and the concentrations of metformin in different blood matrices following oral administration to horses. To that end, six horses received a single 15 g oral dose of metformin and plasma, serum, whole blood, red blood cells, and urine samples were collected starting at 5 min until 31 days post administration. Concentrations of metformin were determined using liquid chromatography-tandem mass spectrometry, and pharmacokinetic analysis performed. Red blood cells act as a reservoir for metformin in horses with the average blood to plasma ratio ranging from 10 at the later time points. The terminal half-life (mean ± SD) was 14.7 ± 7.25, 75.4 ± 32.2 and 49.1 ± 7.01 in plasma, serum, and red blood cells, respectively. The difference between serum and plasma concentrations was > 15% at several time points, especially at the later times. Concentrations in urine samples, fluctuated unpredictably over time. Red blood cells act as a reservoir for metformin leading to a prolonged detection time, necessitating an extended withdrawal time for oral administration prior to competition in performance horses to prevent inadvertent positive drug tests. Additionally, differences in metformin concentrations across various biological matrices may preclude the extrapolation of data from one sample type to another.

Demander à l'IA

Bookmark

View Full Paper