Stability of Ketoprofen Methylester in Plasma of Different Species.

This research paper studies the stability of Ketoprofen Methylester (KME), a prodrug, in the plasma of eight different animal species, and highlights the difference in hydrolytic activities to ester-containing drugs between commercially purchased and freshly collected plasma. It determines the effect of various esterase inhibitors on drug stability as well.

Objective

• The purpose of this study was to observe how stable the prodrug Ketoprofen Methylester (KME) is in the commercially bought and freshly collected plasma of different species—mouse, rat, dog, cat, pig, sheep, cattle, and horse.

Methods

• The researchers evaluated the hydrolysis or breakdown of KME after allowing it to incubate in both commercially bought and freshly collected plasma from the specified animal species.
• In the plasma of rats, dogs, and pigs, various esterase inhibitors were tested for their effectiveness in preventing the breakdown of KME.

Results

• KME was found to be rapidly hydrolyzed in the plasma of mice, rats, and horses—regardless of whether it was commercially bought or freshly collected.
• In cat plasma, the hydrolysis of KME initially happened swiftly and then became limited.
• Minimum hydrolysis of KME was observed in commercially purchased plasma of dogs, pigs, sheep, and cattle, while substantial hydrolysis was recorded in freshly collected plasma from these species.
• The tested esterase inhibitors showed varied effects on the stability of KME in the plasma of rats, dogs, and pigs.

Conclusions

• The findings suggest that plasmas from different species exhibit varied hydrolytic activities towards ester-containing drugs.
• Hydrolytic activities also differed between commercially bought and freshly collected plasma, depending upon the species.
• The use of esterase inhibitors resulted in inconsistent results in preventing the hydrolysis of ester-containing drugs in the plasma across different species.