The pharmacokinetics and in vitro/ex vivo cyclooxygenase selectivity of parecoxib and its active metabolite valdecoxib in cats

- Parecoxib is an injectable prodrug of valdecoxib, a selective inhibitor.
- Parecoxib was rapidly converted to valdecoxib that showed a long half-life.
- The in vitro IC50 values of valdecoxib for COX-2 and COX-1 were 0.45 and 38.6 µM.
- IM injection of 2.5 mg/kg parecoxib selectively inhibited COX-2 in cats.

Parecoxib (PX) is an injectable prodrug of valdecoxib (VX, which is a selective cyclo-oxyganase-2 (COX-2)) inhibitor licensed for humans. The aim of the present study was to evaluate pharmacokinetics and in vitro/ex vivo cyclooxygenase selectivity of PX and VX in cats. In a whole blood in vitro study, PX did not affect either COX enzymes whereas VX revealed a COX-2 selective inhibitory effect in feline whole blood. The IC50 values of VX for COX-2 and COX-1 were 0.45 and 38.6 µM, respectively.Six male cats were treated with 2.5 mg/kg of PX by intramuscular injection. PX was rapidly converted to VX with a relatively short half-life of 0.4 h. VX achieved peak plasma concentration (2.79 ± 1.59 µg/mL) at 7 h following PX injection. The mean residence times for PX and VX were 0.43 ± 0.15 and 5.94 ± 0.88 h, respectively. In the ex vivo study, PX showed a COX-2 inhibition rate of about 70% in samples taken at 1, 2, 4 and 10 h after injection, with a significant difference compared to the control. In contrast, COX-1 was slightly inhibited, ranging from 0.7% to 9.7% of the control inhibition rate without any significant difference for 24 h after PX administration. The preliminary findings of the present research appear promising and encourage further studies to investigate whether PX can be successfully used in feline medicine.