Title:Stability of Ketoprofen Methylester in Plasma of Different Species
Volume: 22
Issue: 3
Author(s): Steven X. Hu*, Kelsey Ernst, Charles P. Benner and Kenneth L. Feenstra
Affiliation:
- Zoetis, Inc., Veterinary Medicine Research and Development, Kalamazoo, MI 49007,United States
Keywords:
Ketoprofen methylester, plasma, stability, species, freshly collected, commercially purchased, esterase inhibition.
Abstract:
Background: Pharmacokinetic and pharmacodynamic assessment of ester-containing drugs can be
impacted by hydrolysis of the drugs in plasma samples post blood collection. The impact is different in the plasma
of different species.
Objective: This study evaluated the stability of a prodrug, ketoprofen methylester (KME), in commercially
purchased and freshly collected plasma of mouse, rat, dog, cat, pig, sheep, cattle and horse.
Methods: KME hydrolysis was determined following its incubation in commercially purchased and freshly collected
plasma of those species. Different esterase inhibitors were evaluated for prevention of the hydrolysis in
rat, dog and pig plasma.
Results: KME was rapidly hydrolyzed in both commercially purchased and freshly collected plasma of mouse,
rat, and horse. The hydrolysis was initially quick and then limited in cat plasma. KME hydrolysis was minimum
in commercially purchased plasma of dog, pig, sheep and cattle but substantial in freshly collected plasma
of those species. Different esterase inhibitors showed different effects on the stability of KME in rat, dog and
pig plasma.
Conclusion: These results indicate that plasma of different species has different hydrolytic activities to estercontaining
drugs. The activities in commercially purchased and freshly collected plasma may be different and
species-dependent. Esterase inhibitors have different effects on preventing hydrolysis of the ester-containing
drugs in the plasma of different species.