Pharmacokinetics of ketoprofen after multiple intravenous doses to mares.

This research investigated how the drug Ketoprofen behaves in the body (pharmacokinetics) of healthy mares after multiple intravenous doses. The findings indicate the ketoprofen concentrations in plasma decreased progressively after each dose with no notable differences between the first and last dose, while the drug’s half-life and clearance rate varied.

Research Methodology and Procedure

• The researchers conducted a study on six healthy mares, administering five daily intravenous doses of 2.2 mg of ketoprofen per kg body weight.
• Through a high-performance liquid chromatographic (HPLC) method, the scientists determined the plasma and urinary ketoprofen concentrations after the first and last dose.
• They also evaluated the rate of urinary excretion of ketoprofen.

Findings

• The study showed that plasma ketoprofen concentrations declined triexponentially after each dose with insignificant differences in plasma concentrations or pharmacokinetic parameter values between the first and last doses.
• The harmonic mean of the terminal elimination half-life of ketoprofen after the first and last dose was 98.2 and 78.0 minutes, respectively.
• Consideration of total plasma clearance and renal clearance values after the first dose showed that they were 4.81 and 1.93 mL/min/kg, respectively.

Excretion of Ketoprofen

• The total plasma clearance of the drug was attributed to renal excretion of ketoprofen and its metabolism to a base-labile conjugate, both of which were excreted in the urine.
• The researchers found that renal clearance of ketoprofen comes from renal tubular secretion as renal clearance was greater than filtration clearance.
• Within the first 420 minutes after the initial dose, approximately 26.4% of the dose was excreted as unconjugated ketoprofen and 29.8% as a base-labile conjugate of ketoprofen. The total urinary recovery of ketoprofen, considering unchanged ketoprofen and from base-labile conjugate, represented 56.2% of the dose.

Plasma Protein Binding of Ketoprofen

• Ketoprofen significantly binds to plasma proteins, with mean plasma protein binding percentages of 92.8% at 500 ng/mL and 91.6% at 10.0 micrograms/mL.