Pharmacokinetics of intra-articular betamethasone sodium phosphate and betamethasone acetate and endogenous hydrocortisone suppression in exercising horses.

This research project studies how the body processes two variations of the steroid betamethasone when used in the joints of exercising horses. The results help understand the timing and quantity of the drug in the blood and urine over the course of six weeks.

Objective and Methodology

• The primary purpose of the study was to understand the pharmacokinetics (the body’s process of absorption, distribution, metabolism, and excretion) of betamethasone sodium phosphate and betamethasone acetate when administered intra-articularly (directly into the joints) in horses that are regularly exercised.
• This study involved eight 4-year-old Thoroughbred mares who were subjected to exercise on a treadmill and were then administered betamethasone intra-articularly.
• The researchers monitored the concentrations of betamethasone and endogenous hydrocortisone (a natural steroid hormone) in the plasma and urine of these horses for a period of six weeks using high performance liquid chromatography-mass spectrometry (HPLC-MS/MS), a highly accurate method to identify and quantify substances in a sample.

Analysis and Findings

• The concentration-time profiles of betamethasone and endogenous hydrocortisone in plasma and urine were used to generate pharmacokinetic estimates. These were then used for comparison among different times and hydrocortisone concentrations.
• The time taken to reach the maximum (peak) concentration of betamethasone was greater in the plasma than in the urine. Similarly, the concentration and the area under the concentration-time curve (AUC, a measure of the drug exposure over time) of betamethasone were greater in urine than in plasma.
• Endogenous hydrocortisone was found to be suppressed in all the horses for at least three days following the administration of betamethasone.
• No significant difference was observed in the time of last quantifiable concentration of betamethasone between plasma and urine.

Significance

• The methodology and highly accurate HPLC-MS/MS assays used in this study enabled early detection and protracted, consistent determination of betamethasone in plasma and urine. This can help in better understanding the effects and the repercussions of betamethasone usage in horses, including the effects it can have on the natural hormone balance in the body.
• These findings could be particularly relevant for the equine industry, specifically in regards to the medical treatment of racehorses and the subsequent monitoring for doping purposes.