Stereospecific pharmacokinetics of free and protein-bound ketoprofen in serum and synovial fluid of horses after intravenous and intramuscular administration.

The researchers conducted a detailed study to understand how horses’ bodies react to the drug ketoprofen, administered through intravenous and intramuscular routes. The investigation focused on the absorption, distribution, and elimination of two different structural forms of the drug, R and S enantiomers, in blood and joint fluid. Unlike many other drugs, these two forms functioned similarly in terms of absorption and interaction with proteins.

Experimental Process

• Six healthy adult mares were selected for the study.
• These horses were administered ketoprofen (2.2 mg/kg of body weight), via both intravenous (i.v) and intramuscular (i.m) routes. The procedure with intramuscular administration was performed three weeks later after the intravenous one.
• Following the drug administration, blood and synovial (joint fluid) samples were collected at regular intervals. These samples were analyzed to determine the concentration of the R and S enantiomers of ketoprofen.
• For this analysis, the researchers utilized a modified reverse-phase stereospecific high-pressure liquid chromatographic method. This technique helped identify and segregate the two ketoprofen enantiomers, R and S.
• The team also examined how these enantiomers interacted with proteins in the blood, using a method called ultrafiltration.
• The entire data were processed using nonlinear least squares methods to calculate pharmacokinetic parameters ie, drug absorption, distribution, metabolism, and excretion values.

Major Findings

• The results showed that after intravenous administration, both enantiomers of ketoprofen fitted best into an open, two-compartment model. This model typically represents the drug’s distribution in the central compartment (blood plasma) and the peripheral compartment (rest of the body).
• The researchers found the relative concentration of the two enantiomers (S-to-R ratio) in the blood to be similar for both intravenous and intramuscular administration.
• However, ketoprofen could only be detected in the joint fluid during the initial three hours after intravenous administration. After this period and after intramuscular administration, the concentrations fell below detectable levels.
• The extent of protein binding was similar for the R and S enantiomers, and it did not seem to be dependent on their concentration in the blood. The adjusted S-to-R serum concentration ratios, accounting for protein binding, were slightly higher than the unadjusted ratios after both types of administration.
• In conclusion, both the R and S enantiomers of ketoprofen get rapidly absorbed, distributed and eliminated in horses, have low volumes of distribution, and show a high degree of protein binding.