Synovial fluid and plasma kinetics of methylprednisolone and methylprednisolone acetate in horses following intra-articular administration of methylprednisolone acetate.

This research paper investigates the behavior of two drugs, methylprednisolone acetate (MPA) and methylprednisolone (MP), in horses after being injected into a joint. It reveals that detectable amounts of MPA last for 2 to 6 days and MP from 4.8 to 39 days in various concentrations, depending on the individual horse.

Studying Drug Kinetics in Horses

• The study focused on the kinetics, or the rate of movement, of MPA and MP in horses. The researchers injected a therapeutic dose of MPA (111 mg in total) into the joint of the horses and monitored its presence and concentration in synovial fluid, the lubricating fluid found within joints.
• They also reviewed the presence of MP, which is derived from the MPA through hydrolysis, a chemical breakdown due to interaction with water.

Investigating the Presence of the Drugs Over Time

• The research team observed the presence of MPA in the synovial fluid of the horses between two to six days post-injection. The peak concentration of MPA was around 2 hours after the injection.
• MP, on the other hand, was found in meaningful concentrations in the synovial fluid for longer durations, between 4.8 to 39 days, possibly due to its slower rate of breakdown. Its maximal concentration was also reached around 2 to 10 hours post-injection.

Looking at Drug Concentration and Effect Over Time

• The researchers observed that the levels of both MPA and MP in the synovial fluid declined rapidly after reaching their peak concentrations.
• The fall in MP’s concentration seemed to happen in two distinct phases. The first phase lasted for five days post-administration, during which the concentration reduced with a half-time of 9.95 hours. The next phase was slower, with a half-time of 115 hours.
• Within the first 24 hours post-injection, trace amounts of MP (less than 5 ng/ml) were also detected in the plasma of the horses.

Evaluating the Impact on Horses’ Health

• In addition to investigating the presence and levels of the drugs in the synovial fluid and plasma, the researchers studied their effect on the health of the horses.
• They found that the levels of hydrocortisone, a hormone that helps the body to respond to stress, were suppressed for three to four days post-injection.
• Despite this, the adrenal glands’ response to adrenocorticotrophic hormone tests, which measure the ability of the adrenal gland to respond to ACTH, remained unaffected.